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SEMINAR
ON
CLUBBING
Presenter : Dr Mahendra
DNB Trainee
Dept : Medicine
Moderator : Dr Barnali B.
NAZARETH HOSPITAL,SHILLONG
THIRSDAY
20/08/2009
CLUBBINGCLUBBING
 Clubbing was described as early as the fifthClubbing was described as early as the fifth
century BC when Hippocrates noted suchcentury BC when Hippocrates noted such
changes in patients suffering from empyema.changes in patients suffering from empyema.
 Hence also called asHence also called as Hippocratic fingerHippocratic finger
 Digital hippocratismDigital hippocratism
 Watch glass nailWatch glass nail
 Drum stick fingerDrum stick finger
 Greeks refers to the sign asGreeks refers to the sign as PlectrodactylyPlectrodactyly
DEFINATIONDEFINATION
 The selective bullous enlargement of the distalThe selective bullous enlargement of the distal
segment of the fingers & toes due tosegment of the fingers & toes due to
proliferation of connective tissue particularlyproliferation of connective tissue particularly
on dorsal surface , is termed as clubbingon dorsal surface , is termed as clubbing
 Tissue at the base of the nail are thickenedTissue at the base of the nail are thickened
and the angle between the nail base and theand the angle between the nail base and the
adjacent skin of finger is obliterated.adjacent skin of finger is obliterated.
 These swelling of nail bed probably caused byThese swelling of nail bed probably caused by
hypervascularity and the opening ofhypervascularity and the opening of
anastomotic channels in the nail bed.anastomotic channels in the nail bed.
 The diagnostic signs comprise:The diagnostic signs comprise:
1 Overcurvature of the nails in the proximal to1 Overcurvature of the nails in the proximal to
distal and transverse planesdistal and transverse planes
2 Enlargement of periungual soft tissue2 Enlargement of periungual soft tissue
structures confined to the tip of each digit.structures confined to the tip of each digit.
CLUBBING OF FINGERSCLUBBING OF FINGERS
CAUSES OF CLUBBINGCAUSES OF CLUBBING
 PULMONARY DISORDERSPULMONARY DISORDERS
1.1. Severe chronic cyanosisSevere chronic cyanosis
2.2. Chronic fibrosing alveolitisChronic fibrosing alveolitis
3.3. EmphysemaEmphysema
4.4. Chronic suppuration in the lungsChronic suppuration in the lungs
- BronchiectasisBronchiectasis
- EmpyemaEmpyema
5.5. Carcinoma of the bronchusCarcinoma of the bronchus
6.6. Pulmonary tuberculosisPulmonary tuberculosis
CAUSES OF CLUBBINGCAUSES OF CLUBBING
 CARDIOVASCULAR DISORDERSCARDIOVASCULAR DISORDERS
1.1. Congenital cyanotic heart diseasesCongenital cyanotic heart diseases
2.2. Infective endocarditisInfective endocarditis
 CHRONIC ABDOMINAL DISORDERSCHRONIC ABDOMINAL DISORDERS
1.1. Crohn’s diseaseCrohn’s disease
2.2. Ulcerative colitisUlcerative colitis
3.3. Polyposis of colonPolyposis of colon
OTHER CAUSESOTHER CAUSES
 ENDOCRINE DISORDERSENDOCRINE DISORDERS
1.1. MyxedemaMyxedema
2.2. Hyperthyroidism (thyroid acropachy)Hyperthyroidism (thyroid acropachy)
3.3. AcromegalyAcromegaly
 HERIDETORYHERIDETORY
 IDIOPATHICIDIOPATHIC
MISCELLANEOUSMISCELLANEOUS

UNILATERAL CLUBBINGUNILATERAL CLUBBING
1.1. Pancoast tumorPancoast tumor
2.2. Subclavian & innominate artery aneurysmSubclavian & innominate artery aneurysm
 UNIDIGITAL CLUBBINGUNIDIGITAL CLUBBING
1.1. TraumaticTraumatic
2.2. GoutGout
3.3. sarcoidosissarcoidosis

ONLY IN UPPER LIMBONLY IN UPPER LIMB
In heroin addicts due to chronic obstructive phlebitisIn heroin addicts due to chronic obstructive phlebitis
unilateral clubbing is seen, also in aneurysm of majorunilateral clubbing is seen, also in aneurysm of major
extremity arteries, with infected arterial graft ,arteriovenousextremity arteries, with infected arterial graft ,arteriovenous
fistulas of brachial vessels.fistulas of brachial vessels.

CLUBBING OF TOESCLUBBING OF TOES
has been associated with an infected abdominal aortichas been associated with an infected abdominal aortic
aneurism & patent ductus arteriosusaneurism & patent ductus arteriosus
GRADESGRADES
1.1. Softening of nail bedSoftening of nail bed
2.2. Obliteration of the angle of the nail bedObliteration of the angle of the nail bed
3.3. Parrot beak or drumstick appearanceParrot beak or drumstick appearance
• Swelling of the subcutaneous tissues over the base of nailSwelling of the subcutaneous tissues over the base of nail
causing the overlying skin to become tense, shiny and wetcausing the overlying skin to become tense, shiny and wet
and increasing the curvature of the nail giving as drumstickand increasing the curvature of the nail giving as drumstick
appearanceappearance..
4.4. Swelling of finger in all dimensions associatedSwelling of finger in all dimensions associated
with hypertrophic pulmonary osteoarthropathywith hypertrophic pulmonary osteoarthropathy
• In this condition there is pain and swelling of hand and wristIn this condition there is pain and swelling of hand and wrist
with radiographic evidence of subperiosteal new bonewith radiographic evidence of subperiosteal new bone
formation.formation.
 It is classified into five phases:It is classified into five phases:
 Phase IPhase I - increase swaftening and fluctuation of the ungual- increase swaftening and fluctuation of the ungual
bed;bed;
 Phase IIPhase II - loss of the natural 15° angle between the nail- loss of the natural 15° angle between the nail
and cuticle;and cuticle;
 Phase IIIPhase III - increased convexity of the ungual bed;- increased convexity of the ungual bed;
 Phase IVPhase IV - clubbed appearance of the digital extremity;- clubbed appearance of the digital extremity;
drumstick appearancedrumstick appearance
 Phase VPhase V - increase of the extremity, with thickening of- increase of the extremity, with thickening of
the distal phalange and longitudinal striationsthe distal phalange and longitudinal striations
on the fingernail.on the fingernail.
Clinical HistoryClinical History
 The development of clubbing usually is gradual enoughThe development of clubbing usually is gradual enough
that many patients are unaware of its presence;that many patients are unaware of its presence;
however, some patients may report swelling of the distalhowever, some patients may report swelling of the distal
portion of the digits, which may be bilateral or unilateralportion of the digits, which may be bilateral or unilateral
or may involve a single digit.or may involve a single digit.
 Although clubbing typically is painless, it rarely mayAlthough clubbing typically is painless, it rarely may
present with pain in the fingertips.present with pain in the fingertips.
 Rapid postoperative resolution of clubbing in a few daysRapid postoperative resolution of clubbing in a few days
was described in a patient with aortic and mitral valvewas described in a patient with aortic and mitral valve
replacement due to infective endocarditisreplacement due to infective endocarditis..
EvaluationEvaluation
 Ask the history aboutAsk the history about
 Respiratory symptomsRespiratory symptoms
 Cardiovascular symptomsCardiovascular symptoms
 Gastrointestinal symptomsGastrointestinal symptoms
 Non specific symptoms such as evening riseNon specific symptoms such as evening rise
temp. anorexia ,wt losstemp. anorexia ,wt loss
 Smoking, alcohol intake, exposure to toxicSmoking, alcohol intake, exposure to toxic
substancessubstances
ExaminationExamination
 To examine for finger clubbing, first look across the nailTo examine for finger clubbing, first look across the nail
and nail bed at the 'nail bed angle'. This is normallyand nail bed at the 'nail bed angle'. This is normally
obtuse but can not be seen in the early stages of fingerobtuse but can not be seen in the early stages of finger
clubbing.clubbing.
 To detect nail bed fluctuation place both thumbs underTo detect nail bed fluctuation place both thumbs under
the pulp of the terminal phalanx and attempt to move thethe pulp of the terminal phalanx and attempt to move the
nail within the nail bed using your index fingers. Anail within the nail bed using your index fingers. A
'spongy feel' confirms nail bed fluctuation.'spongy feel' confirms nail bed fluctuation.
 The sponginess results from increased fibrovascularThe sponginess results from increased fibrovascular
tissue between the nail and the phalanx.tissue between the nail and the phalanx.
Physical findingPhysical finding
 Two objective measures for determining theTwo objective measures for determining the
presence of clubbing have been proposedpresence of clubbing have been proposed
 1. Digital index 2. DPD/IPD1. Digital index 2. DPD/IPD
1.1. Digital indexDigital index
measures 2 separate circumferences on eachmeasures 2 separate circumferences on each
of the 10 fingers at the nail bed (NB) and theof the 10 fingers at the nail bed (NB) and the
distal interphalangeal joint (DIP). The sum ofdistal interphalangeal joint (DIP). The sum of
the 10 ratios (NB:DIP) determines digital indexthe 10 ratios (NB:DIP) determines digital index
If it is more than 10, it signifies the clubbing.If it is more than 10, it signifies the clubbing.
22 Another method to detectAnother method to detect
clubbing is measurementclubbing is measurement
of the phalangeal depthof the phalangeal depth
ratio ( DPD/IPD )ratio ( DPD/IPD )
 In a normal finger it is <1,In a normal finger it is <1,
the distal phalangealthe distal phalangeal
depth is smaller than thedepth is smaller than the
interphalangeal depth.interphalangeal depth.
 In clubbing thisIn clubbing this
relationship is reversedrelationship is reversed
(>1).(>1).
 The measurement canThe measurement can
easily be taken using aeasily be taken using a
calipercaliper
Profile signProfile sign
 The degree of the deformity may be measured byThe degree of the deformity may be measured by
Lovibond’s ‘profile sign’ which measures the angleLovibond’s ‘profile sign’ which measures the angle
between the curved nail plate and the proximal nail foldbetween the curved nail plate and the proximal nail fold
 This is normally 160°, but exceeds 180° in clubbing.This is normally 160°, but exceeds 180° in clubbing.

A modified profile sign is assessed by measuring theA modified profile sign is assessed by measuring the
angle between the middle and the terminal phalanx atangle between the middle and the terminal phalanx at
the interphalangeal joint: in normal fingers the distalthe interphalangeal joint: in normal fingers the distal
phalanx forms an almost straight (180°) extension of thephalanx forms an almost straight (180°) extension of the
middle phalanx, whereas in severe clubbing this anglemiddle phalanx, whereas in severe clubbing this angle
may be reduced to160° or even 140°.may be reduced to160° or even 140°.
Schamroth’s signSchamroth’s sign
 The best indicator may beThe best indicator may be
the simple clinical methodthe simple clinical method
adopted by Schamroth:adopted by Schamroth:
 In normal individuals aIn normal individuals a
distinct aperture ordistinct aperture or
schamroth’s window,schamroth’s window,
usually diamond-shaped,usually diamond-shaped,
is formed at the base ofis formed at the base of
the nail bed when twothe nail bed when two
fingers held together withfingers held together with
nails facing each other.nails facing each other.
 Early clubbing obliteratesEarly clubbing obliterates
this window.this window.
 INTERESTIG thing is that Schamroth not onlyINTERESTIG thing is that Schamroth not only
described the sign but himself was the patient.described the sign but himself was the patient.
 In a report published back in 1976 ,he describedIn a report published back in 1976 ,he described
not only his 3 attacks of infective endocarditisnot only his 3 attacks of infective endocarditis
,but also the clinical sign that bears his name.,but also the clinical sign that bears his name.
“Schamroth’ sign.”“Schamroth’ sign.”
CLASSIFICATIONCLASSIFICATION
NormalNormal MildMild ModerateModerate SevereSevere
DPD/IPDDPD/IPD <1<1 >1>1 >1>1 >1>1
Profile AngleProfile Angle <160<160 <180<180 =180=180 >180>180
Fishman classified clubbing in to following
category by using ratio of distal phalangeal
distance &inter phalangeal distance & Profile
angle that is angle between nail bed and nail
PathophisiologyPathophisiology
 The specific pathophysiologic mechanism ofThe specific pathophysiologic mechanism of
digital clubbing remains unknown. Many theoriesdigital clubbing remains unknown. Many theories
have been proposed, yet none have receivedhave been proposed, yet none have received
widespread acceptance as a comprehensivewidespread acceptance as a comprehensive
explanation for the phenomenon of digitalexplanation for the phenomenon of digital
clubbing.clubbing.
 As stated best by Samuel West in 1897,As stated best by Samuel West in 1897,
"Clubbing is one of those phenomena with which"Clubbing is one of those phenomena with which
we are all so familiar that we appear to knowwe are all so familiar that we appear to know
more about it than we really do."more about it than we really do."
 Theories suggested for theTheories suggested for the
pathogenesis of Hypertrophicpathogenesis of Hypertrophic
osteoarthropathy & clubbingosteoarthropathy & clubbing
1.1. NeurogenicNeurogenic
2.2. HumoralHumoral
3.3. Role of megakaryocytes and largeRole of megakaryocytes and large
platelet particlesplatelet particles
4.4. Genetic & familialGenetic & familial
5.5. HypoxiaHypoxia
NEUROGENICNEUROGENIC
 Based on the observation that vagotomyBased on the observation that vagotomy
resulted in symptomatic improvement in theresulted in symptomatic improvement in the
small number of pt of lung tumors & HOA,small number of pt of lung tumors & HOA,
 It was postulated that afferent vagal stimuli fromIt was postulated that afferent vagal stimuli from
the tumor site led via intercostal nerves / vagi tothe tumor site led via intercostal nerves / vagi to
brainstem from where efferent nerve impulsesbrainstem from where efferent nerve impulses
to terminal /distal extremities causingto terminal /distal extremities causing
vasodilatation and resulting in changes thatvasodilatation and resulting in changes that
leads to HOA.leads to HOA.
 But this theory cant explain the clubbing inBut this theory cant explain the clubbing in
condition where vagal stimulation not occurs.condition where vagal stimulation not occurs.
HUMORALHUMORAL
 Humoral theory postulated that solubleHumoral theory postulated that soluble
substances that’s are normally inactivated orsubstances that’s are normally inactivated or
removed during passage through the lungremoved during passage through the lung
reached the systemic circulation in an activereached the systemic circulation in an active
form and stimulated the changes of HOA .( pg,form and stimulated the changes of HOA .( pg,
bradykinin, estrogen, ferritin, gh)bradykinin, estrogen, ferritin, gh)
 But it is found that the level of such substancesBut it is found that the level of such substances
in serum does not differ from normal individual.in serum does not differ from normal individual.
Megakaryocytes + large platelet particle
Bypass lung
Reach distal extremities
Interact with endothelial cells
Release of PDGF
Stimulation of fibroblast
TGF-β
Proliferation of connective tissues &
Periostium
SHUNT THEORYSHUNT THEORY
GENETICGENETIC
 A mutation in theA mutation in the HPGDHPGD gene encodinggene encoding
nicotinamide (NAD)+ –dependent 15-nicotinamide (NAD)+ –dependent 15-
hydroxyprostaglandin dehydrogenasehydroxyprostaglandin dehydrogenase
was identified in a largewas identified in a large
Pakistani family with isolated congenital nail clubbing.Pakistani family with isolated congenital nail clubbing.
 Clubbing is a feature of Pachydermoperiostosis (PDP), aClubbing is a feature of Pachydermoperiostosis (PDP), a
rare genodermatosis usually an autosomal dominantrare genodermatosis usually an autosomal dominant
model with incomplete penetrance and variablemodel with incomplete penetrance and variable
expression, but also both autosomal recessive and X-expression, but also both autosomal recessive and X-
linked inheritance have been suggested in some PDPlinked inheritance have been suggested in some PDP
families.families.
HPGD & PGE2HPGD & PGE2
 Importantly, 15-hydroxyprostaglandinImportantly, 15-hydroxyprostaglandin
dehydrogenase is the main enzyme responsibledehydrogenase is the main enzyme responsible
for breaking down offor breaking down of prostaglandin E2prostaglandin E2
(PGE2, a lipid compound which has a number of(PGE2, a lipid compound which has a number of
functions in the lung, the GI tract, and in thefunctions in the lung, the GI tract, and in the
uterus during pregnancy) and otheruterus during pregnancy) and other
prostaglandins and related compounds.prostaglandins and related compounds.
 Gene responsible for HPGD is located onGene responsible for HPGD is located on
chromosome 4 q34chromosome 4 q34
 HPGD, the key enzyme in prostaglandin degradation,HPGD, the key enzyme in prostaglandin degradation,
PGE2 is known to have a number of effects upon bone.PGE2 is known to have a number of effects upon bone.
 Mutations in the key enzyme of prostaglandinMutations in the key enzyme of prostaglandin
degradation lead to PHO, suggests that elevateddegradation lead to PHO, suggests that elevated
prostaglandin levels are critical in causing the muchprostaglandin levels are critical in causing the much
more common clubbing seen in pulmonary hypertrophicmore common clubbing seen in pulmonary hypertrophic
osteoarthropathyosteoarthropathy
 As the lung is known to be a site of PGE2 clearance byAs the lung is known to be a site of PGE2 clearance by
HPGD, perhaps the lung diseases associated withHPGD, perhaps the lung diseases associated with
pulmonary hypertrophic osteoarthropathy lead topulmonary hypertrophic osteoarthropathy lead to
decreased clearance and degradation of PGE2.decreased clearance and degradation of PGE2.
 This association also seen in PDA.This association also seen in PDA.
 Structural model of PGE2Structural model of PGE2
bound to HPGD (Colinbound to HPGD (Colin
Fishwick, School ofFishwick, School of
Chemistry, Leeds),Chemistry, Leeds),
showing the predictedshowing the predicted
effect of the PHOeffect of the PHO
mutation A140P,mutation A140P,
displacing the substratedisplacing the substrate
and preventingand preventing
coordination of its 15-OHcoordination of its 15-OH
group to serine 138.group to serine 138.
HYPOXYAHYPOXYA
 Hypoxia has been proposed as an alternativeHypoxia has been proposed as an alternative
explanation for clubbing in cyanotic heartexplanation for clubbing in cyanotic heart
disease and pulmonary diseases.disease and pulmonary diseases.
 An increase in hypoxia may activate localAn increase in hypoxia may activate local
vasodilators, consequently increasing blood flowvasodilators, consequently increasing blood flow
to the distal portion of the digits that leads toto the distal portion of the digits that leads to
hypertrophy of fibroconective tissue of nail bed.hypertrophy of fibroconective tissue of nail bed.
 However, in most cases, hypoxia is absent in theHowever, in most cases, hypoxia is absent in the
presence of clubbing, and many diseases withpresence of clubbing, and many diseases with
noted hypoxia are not associated with clubbingnoted hypoxia are not associated with clubbing
 There are three main types of clubbing:There are three main types of clubbing:
 1 Simple clubbing.1 Simple clubbing.
 2 Hypertrophic pulmonary osteoarthropathy.2 Hypertrophic pulmonary osteoarthropathy.
 3 Pachydermoperiostosis.3 Pachydermoperiostosis.
Simple clubbingSimple clubbing
 characteristics:characteristics:
 Increased nail curvature occurs with a transverse furrowIncreased nail curvature occurs with a transverse furrow
separating it from the rest of the nail both in the early stageseparating it from the rest of the nail both in the early stage
and after resolution. The onset is usually gradual andand after resolution. The onset is usually gradual and
painless,painless, except in some cases of carcinoma of the lung in which clubbingexcept in some cases of carcinoma of the lung in which clubbing
may develop abruptly and be associated with severe painmay develop abruptly and be associated with severe pain..
 Hypertrophy of the soft parts of the terminal segment causedHypertrophy of the soft parts of the terminal segment caused
by firm, elastic, oedematous infiltration of the pulp, whichby firm, elastic, oedematous infiltration of the pulp, which
may spread to the dorsal surface with marked periungualmay spread to the dorsal surface with marked periungual
swelling.swelling.
 Hyperplasia of the dermal fibro vascular tissue may extendHyperplasia of the dermal fibro vascular tissue may extend
to involve the adjacent matrix.to involve the adjacent matrix. This accounts for one of the earliestThis accounts for one of the earliest
signs of clubbing—abnormal mobility of the nail base, which can be rocked backsigns of clubbing—abnormal mobility of the nail base, which can be rocked back
and forth giving the impression that it is floating on a soft oedematous padand forth giving the impression that it is floating on a soft oedematous pad..
 Acral cyanosis is often observedAcral cyanosis is often observed
Hypertrophic pulmonary osteoarthropathyHypertrophic pulmonary osteoarthropathy
 Clubbing of the nails.Clubbing of the nails.
 Hypertrophy of the upper and lower extremitiesHypertrophy of the upper and lower extremities
 Joint changes with pseudo-inflammatory, symmetrical,Joint changes with pseudo-inflammatory, symmetrical,
painful arthropathy of the large joints, especially thosepainful arthropathy of the large joints, especially those
of the legs.of the legs. This syndrome is almost pathognomonic of lung carcinoma andThis syndrome is almost pathognomonic of lung carcinoma and
mesothelioma of the pleura; less commonly bronchiectasis . Along with thismesothelioma of the pleura; less commonly bronchiectasis . Along with this
Gynaecomastia may also be present.Gynaecomastia may also be present.
 There may bilateral, proliferative periostitis andThere may bilateral, proliferative periostitis and
moderate, diffuse decalcification of bone.moderate, diffuse decalcification of bone.
 Peripheral neurovascular disorders such as localPeripheral neurovascular disorders such as local
cyanosis and paraesthesia are not uncommoncyanosis and paraesthesia are not uncommon
PachydermoperiostosisPachydermoperiostosis
(( primary hypertrophic osteoarthropathy )primary hypertrophic osteoarthropathy )
 The digital changes typically begin at or about the time ofThe digital changes typically begin at or about the time of
puberty.puberty.
 Autosomal dominant trait, nine times more common in boysAutosomal dominant trait, nine times more common in boys
than girls.than girls.
 The ends of the fingers and toes are bulbous and often clubThe ends of the fingers and toes are bulbous and often club
shaped, with hyperhidrosis of the hands and the feetshaped, with hyperhidrosis of the hands and the feet
 The clubbing stops abruptly at the distal interphalangeal joint.The clubbing stops abruptly at the distal interphalangeal joint.
the finger tips are clinically identical to those of hypertrophic pulmonarythe finger tips are clinically identical to those of hypertrophic pulmonary
osteoarthropathy.osteoarthropathy.
 However, in Pachydermoperiostosis the thickened cortexHowever, in Pachydermoperiostosis the thickened cortex
appears homogeneous on X-ray examination and does notappears homogeneous on X-ray examination and does not
impinge on the medullary spaceimpinge on the medullary space..
 Acro-osteolysis of theAcro-osteolysis of the
distal phalanges hasdistal phalanges has
been reported.been reported.
 The pachydermal changeThe pachydermal change
of the extremities andof the extremities and
face, with furrowing onface, with furrowing on
forehead and greasy skin,forehead and greasy skin,
cutis verticis gyrata is thecutis verticis gyrata is the
most characteristicmost characteristic
feature of the disorder; itfeature of the disorder; it
is termed the Touraine-is termed the Touraine-
Solente-Golé syndrome.Solente-Golé syndrome.
Clubbing
THYROID ACROPACHYTHYROID ACROPACHY
 Hyperthyroidism graves disease treated or untreatedHyperthyroidism graves disease treated or untreated
occasionally associated with clubbing & periostitis ofoccasionally associated with clubbing & periostitis of
the bones of the feet & hands. This condition knownthe bones of the feet & hands. This condition known
as thyroid acropachyas thyroid acropachy
 Periostitis is asymptomatic, occurs at midshaft & diaphysealPeriostitis is asymptomatic, occurs at midshaft & diaphyseal
portion of metacarpals & phalangeal bones.portion of metacarpals & phalangeal bones.
 Elevated levels of long acting thyroid stimulator are found inElevated levels of long acting thyroid stimulator are found in
the serum of these patients.the serum of these patients.
Clubbing
CausesCauses
 Idiopathic or primary clubbingIdiopathic or primary clubbing
 Pachydermoperiostisis Clubbing is seen inPachydermoperiostisis Clubbing is seen in
89% cases of PDP,89% cases of PDP,
 familial clubbing,familial clubbing,
 Secondary hypertrophic osteoarthropathySecondary hypertrophic osteoarthropathy
Causes of secondary clubbingCauses of secondary clubbing
include the following :include the following :
 Pulmonary disease – 80%Pulmonary disease – 80%
 Lung cancer,Lung cancer,
 cystic fibrosis,cystic fibrosis,
 interstitial lung disease,interstitial lung disease,
 idiopathic pulmonary fibrosis,idiopathic pulmonary fibrosis,
 sarcoidosis,sarcoidosis,
 Bronchiectasis , empyema,Bronchiectasis , empyema,
 TuberculosisTuberculosis
 Pleural mesothelioma, pulmonary artery sarcoma,Pleural mesothelioma, pulmonary artery sarcoma,
cryptogenic fibrosing alveolitis, and pulmonarycryptogenic fibrosing alveolitis, and pulmonary
metastasesmetastases
 Cardiac disease –Cardiac disease –
 Cyanotic congenital heart disease,Cyanotic congenital heart disease,
 other causes of right-to-left shunting,other causes of right-to-left shunting,
 and bacterial endocarditisand bacterial endocarditis
 Gastrointestinal disease –Gastrointestinal disease –
 Ulcerative colitis,Ulcerative colitis,
 Crohn's disease 38%,Crohn's disease 38%,
 Primary biliary cirrhosis,Primary biliary cirrhosis,
 Cirrhosis of the liver,Cirrhosis of the liver,
 Leiomyoma of the esophagus, achalasia,Leiomyoma of the esophagus, achalasia,
 And peptic ulceration of the esophagusAnd peptic ulceration of the esophagus
 Malignancies –Malignancies –
 Thyroid cancer,Thyroid cancer,
 Thymus cancer,Thymus cancer,
 Hodgkin disease,Hodgkin disease,
 Disseminated chronic myeloid leukemiaDisseminated chronic myeloid leukemia
 POEMSPOEMS
 [polyneuropathy, organomegaly, endocrinopathy,[polyneuropathy, organomegaly, endocrinopathy,
monoclonal gammopathy, and skin changes]monoclonal gammopathy, and skin changes]
 POEMSPOEMS
 [[polyneuropathy, organomegaly, endocrinopathy, monoclonalpolyneuropathy, organomegaly, endocrinopathy, monoclonal
gammopathy, and skin changesgammopathy, and skin changes] syndrome is a rare] syndrome is a rare
paraneoplastic syndrome secondary to a plasma cellparaneoplastic syndrome secondary to a plasma cell
dyscrasia in which clubbing may be seen.dyscrasia in which clubbing may be seen.
 Other findings including peripheral neuropathy,Other findings including peripheral neuropathy,
organomegaly, endocrinopathy, monoclonalorganomegaly, endocrinopathy, monoclonal
plasma proliferative disorder, skin changes,plasma proliferative disorder, skin changes,
sclerotic bone lesions, Castleman disease,sclerotic bone lesions, Castleman disease,
thrombocytosis, papilledema, peripheral edema,thrombocytosis, papilledema, peripheral edema,
pleural effusions, ascites, and white nailpleural effusions, ascites, and white nail
 Miscellaneous conditions –Miscellaneous conditions –
 Acromegaly,Acromegaly,
 Thyroid acropachy,Thyroid acropachy,
 Pregnancy ,Pregnancy ,
 An unusual complication of severe secondaryAn unusual complication of severe secondary
hyperparathyroidism,hyperparathyroidism,
 Hypoxemia possibly related to long-termHypoxemia possibly related to long-term
smoking of cannabissmoking of cannabis
 Occupational acro-osteolysis (exposure toOccupational acro-osteolysis (exposure to
vinyl chloride).vinyl chloride).
Drumstick appearanceDrumstick appearance
 Clubbing in toes seen in infected abdominal aneurismClubbing in toes seen in infected abdominal aneurism
(1) Psuedoclubbing in trauma (2) in case of Acromegaly (3) clubbing
Hook nail deformity
Psuedoclubing in yellow nail syndrome
Histological FindingsHistological Findings
 Microscopically,Microscopically,
 The collagen fibrils and cells are separated by aThe collagen fibrils and cells are separated by a
distance greater than that seen in histologicallydistance greater than that seen in histologically
normal specimens. This increased separation resultsnormal specimens. This increased separation results
in a less dense nail bed matrixin a less dense nail bed matrix
 Primitive fibroblasts are seen with large nuclei,Primitive fibroblasts are seen with large nuclei,
basophilic cytoplasm, and long reticular processes.basophilic cytoplasm, and long reticular processes.
 Increased and scattered extra vascular lymphocytesIncreased and scattered extra vascular lymphocytes
and, less often, a moderately increased number ofand, less often, a moderately increased number of
tissue eosinophils also are noted in the nail beds oftissue eosinophils also are noted in the nail beds of
some specimens.some specimens.
 The Periostium of the nail bed may be thickened withThe Periostium of the nail bed may be thickened with
increased vascular penetration.increased vascular penetration.
 Eventually, increased collagen is laid down in allEventually, increased collagen is laid down in all
types of chronic clubbing. The mat of collagen fiberstypes of chronic clubbing. The mat of collagen fibers
may be abnormally thick and dense. The walls of themay be abnormally thick and dense. The walls of the
vascular components increase in thickness and arevascular components increase in thickness and are
encased in a thick fibrous sheet. At this stage ofencased in a thick fibrous sheet. At this stage of
clubbing, the histologic and morphologic changesclubbing, the histologic and morphologic changes
probably are irreversibleprobably are irreversible
INVESTIGATIONINVESTIGATION
 Laboratory StudiesLaboratory Studies
 Because clubbing typically is secondary to anBecause clubbing typically is secondary to an
underlying pathological process, performunderlying pathological process, perform
pertinent laboratory studies for primarypertinent laboratory studies for primary
medical disorders that are suggested clinicallymedical disorders that are suggested clinically
 Imaging StudiesImaging Studies
 Radiographic studies include bone dissolution, bone formation,Radiographic studies include bone dissolution, bone formation,
or no change in the bone of the distal phalanx.or no change in the bone of the distal phalanx.
 The types of changes may depend on the underlyingThe types of changes may depend on the underlying
pathological processes, as well as the duration of the processes.pathological processes, as well as the duration of the processes.
 The lysis of bone predominates in the digits of patients withThe lysis of bone predominates in the digits of patients with
congenital cyanotic heart disease, while hypertrophycongenital cyanotic heart disease, while hypertrophy
predominates in the digits of patients with clubbing secondary topredominates in the digits of patients with clubbing secondary to
pulmonary conditions.pulmonary conditions.
 As an alternate view, hypertrophy may occur earlier in theAs an alternate view, hypertrophy may occur earlier in the
process of clubbing, and, eventually, it may change to osteolysisprocess of clubbing, and, eventually, it may change to osteolysis
as the process becomes chronic.as the process becomes chronic.
 Radiograph of both handsRadiograph of both hands
in a 42-year-old man within a 42-year-old man with
a family history ofa family history of
primary hypertrophicprimary hypertrophic
osteoarthropathy who hadosteoarthropathy who had
coarsened facial featurescoarsened facial features
and thickness of the scalp.and thickness of the scalp.
 Note the soft tissueNote the soft tissue
clubbing and acro-clubbing and acro-
osteolysis of the terminalosteolysis of the terminal
phalanges.phalanges.
Radiograph showing thickened, columnarRadiograph showing thickened, columnar
diaphyses and erosion of the terminaldiaphyses and erosion of the terminal
phalangeal tufts in PHOphalangeal tufts in PHO..
 Technetium Tc 99m skeletal imagingTechnetium Tc 99m skeletal imaging
 may be helpful in determining the presencemay be helpful in determining the presence
and extent of bone changes in clubbed digits,and extent of bone changes in clubbed digits,
which show increased uptake of thewhich show increased uptake of the
radionuclide.radionuclide.
 The increased, intense, symmetric uptakeThe increased, intense, symmetric uptake
typically is localized to the nail beds and maytypically is localized to the nail beds and may
result from increased blood flow and changesresult from increased blood flow and changes
in the surrounding soft tissuesin the surrounding soft tissues
 Radionuclide scansRadionuclide scans
show the typicalshow the typical
appearance ofappearance of
secondarysecondary
hypertrophichypertrophic
osteoarthropathyosteoarthropathy
caused by acaused by a
bronchogenicbronchogenic
carcinoma.carcinoma.
 ThermographyThermography
 It is another imaging modality being studiedIt is another imaging modality being studied
for use in diagnosis and monitoring of patientsfor use in diagnosis and monitoring of patients
with digital clubbing.with digital clubbing.
 Patients may show increased temperature inPatients may show increased temperature in
the distal digits, which can be attributed to anthe distal digits, which can be attributed to an
increase in blood flow secondary toincrease in blood flow secondary to
vasodilation.vasodilation.
 Not all patients with clubbing have positiveNot all patients with clubbing have positive
thermographic resultsthermographic results
 Positron emission tomographyPositron emission tomography
 It also has been used to study the glucose metabolism ofIt also has been used to study the glucose metabolism of
clubbed digits. An increased signal, indicating increased glucoseclubbed digits. An increased signal, indicating increased glucose
metabolism, has been demonstrated in the distal part of themetabolism, has been demonstrated in the distal part of the
clubbed fingers. These changes are not seen in fingertips withclubbed fingers. These changes are not seen in fingertips with
normal morphology. The increase in signal supports the theorynormal morphology. The increase in signal supports the theory
that clubbing is caused by the presence of a factor (eg, platelet-that clubbing is caused by the presence of a factor (eg, platelet-
derived growth factor) that increases cellular metabolism.derived growth factor) that increases cellular metabolism.
 Other imaging studies, such as computed tomography orOther imaging studies, such as computed tomography or
magnetic resonance imaging, may be helpful inmagnetic resonance imaging, may be helpful in
evaluating the patient for the primary pathologicalevaluating the patient for the primary pathological
process causing the clubbing.process causing the clubbing.
TreatmentTreatment
 Medical CareMedical Care
 No specific treatment for clubbing is available.No specific treatment for clubbing is available.
Treatment of the underlying pathologicalTreatment of the underlying pathological
condition may decrease the clubbing or,condition may decrease the clubbing or,
potentially, reverse it if performed earlypotentially, reverse it if performed early
enough. Once substantial chronic tissueenough. Once substantial chronic tissue
changes, including increased collagenchanges, including increased collagen
deposition, have occurred, reversal is unlikely.deposition, have occurred, reversal is unlikely.
 Treatment for related problems, such as pain,Treatment for related problems, such as pain,
is symptomatic.is symptomatic.
 Surgical CareSurgical Care
 No specific surgical procedures are performedNo specific surgical procedures are performed
for clubbing. Appropriate surgical treatment offor clubbing. Appropriate surgical treatment of
underlying disease, such as tumor removal inunderlying disease, such as tumor removal in
patients with lung cancer, may improve orpatients with lung cancer, may improve or
reverse clubbing, provided that permanentreverse clubbing, provided that permanent
morphologic changes have not occurredmorphologic changes have not occurred..
 Medico legal PitfallsMedico legal Pitfalls
 Failure to perform a thorough and exhaustiveFailure to perform a thorough and exhaustive
workup of the patient who presents withworkup of the patient who presents with
clubbing of the nails since clubbing is aclubbing of the nails since clubbing is a
physical finding associated with many severephysical finding associated with many severe
disease processes, including severaldisease processes, including several
malignanciesmalignancies
 ReferencesReferences
 Harrison's principals of internal medicine,Harrison's principals of internal medicine,
 Hutchison’s clinical methodsHutchison’s clinical methods
 Macleod's clinical methodMacleod's clinical method
 Crofton & Douglus Respiratory diseasesCrofton & Douglus Respiratory diseases
 P J Mehta’s practical medicineP J Mehta’s practical medicine
 British medical journalBritish medical journal
 Internet emedicine.comInternet emedicine.com
 Goyal S, Griffiths AD, Omarouayache S, Mohammedi R. An improved method of studying fingernailGoyal S, Griffiths AD, Omarouayache S, Mohammedi R. An improved method of studying fingernail
morphometry: application to the early detection of fingernail clubbing.morphometry: application to the early detection of fingernail clubbing. J Am AcadJ Am Acad
DermatolDermatol. Oct 1998;39(4 Pt 1):640-2.. Oct 1998;39(4 Pt 1):640-2.
 Castori M, Sinibaldi L, Mingarelli R, Lachman RS, Rimoin DL, DallapiccolaCastori M, Sinibaldi L, Mingarelli R, Lachman RS, Rimoin DL, Dallapiccola
B. Pachydermoperiostosis: an update.B. Pachydermoperiostosis: an update. Clin GenetClin Genet. Dec 2005;68(6):477-86.. Dec 2005;68(6):477-86.
 Tariq M, Azeem Z, Ali G, Chishti MS, Ahmad W. Mutation in the HPGD gene encoding NAD+Tariq M, Azeem Z, Ali G, Chishti MS, Ahmad W. Mutation in the HPGD gene encoding NAD+
dependent 15-hydroxyprostaglandin dehydrogenase underlies isolated congenital nail clubbingdependent 15-hydroxyprostaglandin dehydrogenase underlies isolated congenital nail clubbing
(ICNC).(ICNC). J Med GenetJ Med Genet. Jan 2009;46(1):14-20.. Jan 2009;46(1):14-20.
 Dickinson CJ, Martin JF. Megakaryocytes and platelet clumps as the cause of fingerDickinson CJ, Martin JF. Megakaryocytes and platelet clumps as the cause of finger
clubbing.clubbing. LancetLancet. Dec 19 1987;2(8573):1434-5.. Dec 19 1987;2(8573):1434-5.
 Ddungu H, Johnson JL, Smieja M, Mayanja-Kizza H. Digital clubbing in tuberculosis--relationshipDdungu H, Johnson JL, Smieja M, Mayanja-Kizza H. Digital clubbing in tuberculosis--relationship
to HIV infection, extent of disease and hypoalbuminemia.to HIV infection, extent of disease and hypoalbuminemia. BMC Infect DisBMC Infect Dis. Mar 10 2006;6:45.. Mar 10 2006;6:45.
THANK YOU
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Clubbing

  • 1. seminarseminar Rgdtwwy vbfhejsRgdtwwy vbfhejs Maksjdue; najsuMaksjdue; najsu Cbdgawue ndhfgw dhskdrCbdgawue ndhfgw dhskdr Sbdgejfhrtgfbxmw msdjfhrytoaswSbdgejfhrtgfbxmw msdjfhrytoasw nfgdsnfgds SEMINAR ON CLUBBING Presenter : Dr Mahendra DNB Trainee Dept : Medicine Moderator : Dr Barnali B. NAZARETH HOSPITAL,SHILLONG THIRSDAY 20/08/2009
  • 2. CLUBBINGCLUBBING  Clubbing was described as early as the fifthClubbing was described as early as the fifth century BC when Hippocrates noted suchcentury BC when Hippocrates noted such changes in patients suffering from empyema.changes in patients suffering from empyema.  Hence also called asHence also called as Hippocratic fingerHippocratic finger  Digital hippocratismDigital hippocratism  Watch glass nailWatch glass nail  Drum stick fingerDrum stick finger  Greeks refers to the sign asGreeks refers to the sign as PlectrodactylyPlectrodactyly
  • 3. DEFINATIONDEFINATION  The selective bullous enlargement of the distalThe selective bullous enlargement of the distal segment of the fingers & toes due tosegment of the fingers & toes due to proliferation of connective tissue particularlyproliferation of connective tissue particularly on dorsal surface , is termed as clubbingon dorsal surface , is termed as clubbing  Tissue at the base of the nail are thickenedTissue at the base of the nail are thickened and the angle between the nail base and theand the angle between the nail base and the adjacent skin of finger is obliterated.adjacent skin of finger is obliterated.  These swelling of nail bed probably caused byThese swelling of nail bed probably caused by hypervascularity and the opening ofhypervascularity and the opening of anastomotic channels in the nail bed.anastomotic channels in the nail bed.
  • 4.  The diagnostic signs comprise:The diagnostic signs comprise: 1 Overcurvature of the nails in the proximal to1 Overcurvature of the nails in the proximal to distal and transverse planesdistal and transverse planes 2 Enlargement of periungual soft tissue2 Enlargement of periungual soft tissue structures confined to the tip of each digit.structures confined to the tip of each digit.
  • 6. CAUSES OF CLUBBINGCAUSES OF CLUBBING  PULMONARY DISORDERSPULMONARY DISORDERS 1.1. Severe chronic cyanosisSevere chronic cyanosis 2.2. Chronic fibrosing alveolitisChronic fibrosing alveolitis 3.3. EmphysemaEmphysema 4.4. Chronic suppuration in the lungsChronic suppuration in the lungs - BronchiectasisBronchiectasis - EmpyemaEmpyema 5.5. Carcinoma of the bronchusCarcinoma of the bronchus 6.6. Pulmonary tuberculosisPulmonary tuberculosis
  • 7. CAUSES OF CLUBBINGCAUSES OF CLUBBING  CARDIOVASCULAR DISORDERSCARDIOVASCULAR DISORDERS 1.1. Congenital cyanotic heart diseasesCongenital cyanotic heart diseases 2.2. Infective endocarditisInfective endocarditis  CHRONIC ABDOMINAL DISORDERSCHRONIC ABDOMINAL DISORDERS 1.1. Crohn’s diseaseCrohn’s disease 2.2. Ulcerative colitisUlcerative colitis 3.3. Polyposis of colonPolyposis of colon
  • 8. OTHER CAUSESOTHER CAUSES  ENDOCRINE DISORDERSENDOCRINE DISORDERS 1.1. MyxedemaMyxedema 2.2. Hyperthyroidism (thyroid acropachy)Hyperthyroidism (thyroid acropachy) 3.3. AcromegalyAcromegaly  HERIDETORYHERIDETORY  IDIOPATHICIDIOPATHIC
  • 9. MISCELLANEOUSMISCELLANEOUS  UNILATERAL CLUBBINGUNILATERAL CLUBBING 1.1. Pancoast tumorPancoast tumor 2.2. Subclavian & innominate artery aneurysmSubclavian & innominate artery aneurysm  UNIDIGITAL CLUBBINGUNIDIGITAL CLUBBING 1.1. TraumaticTraumatic 2.2. GoutGout 3.3. sarcoidosissarcoidosis  ONLY IN UPPER LIMBONLY IN UPPER LIMB In heroin addicts due to chronic obstructive phlebitisIn heroin addicts due to chronic obstructive phlebitis unilateral clubbing is seen, also in aneurysm of majorunilateral clubbing is seen, also in aneurysm of major extremity arteries, with infected arterial graft ,arteriovenousextremity arteries, with infected arterial graft ,arteriovenous fistulas of brachial vessels.fistulas of brachial vessels.  CLUBBING OF TOESCLUBBING OF TOES has been associated with an infected abdominal aortichas been associated with an infected abdominal aortic aneurism & patent ductus arteriosusaneurism & patent ductus arteriosus
  • 10. GRADESGRADES 1.1. Softening of nail bedSoftening of nail bed 2.2. Obliteration of the angle of the nail bedObliteration of the angle of the nail bed 3.3. Parrot beak or drumstick appearanceParrot beak or drumstick appearance • Swelling of the subcutaneous tissues over the base of nailSwelling of the subcutaneous tissues over the base of nail causing the overlying skin to become tense, shiny and wetcausing the overlying skin to become tense, shiny and wet and increasing the curvature of the nail giving as drumstickand increasing the curvature of the nail giving as drumstick appearanceappearance.. 4.4. Swelling of finger in all dimensions associatedSwelling of finger in all dimensions associated with hypertrophic pulmonary osteoarthropathywith hypertrophic pulmonary osteoarthropathy • In this condition there is pain and swelling of hand and wristIn this condition there is pain and swelling of hand and wrist with radiographic evidence of subperiosteal new bonewith radiographic evidence of subperiosteal new bone formation.formation.
  • 11.  It is classified into five phases:It is classified into five phases:  Phase IPhase I - increase swaftening and fluctuation of the ungual- increase swaftening and fluctuation of the ungual bed;bed;  Phase IIPhase II - loss of the natural 15° angle between the nail- loss of the natural 15° angle between the nail and cuticle;and cuticle;  Phase IIIPhase III - increased convexity of the ungual bed;- increased convexity of the ungual bed;  Phase IVPhase IV - clubbed appearance of the digital extremity;- clubbed appearance of the digital extremity; drumstick appearancedrumstick appearance  Phase VPhase V - increase of the extremity, with thickening of- increase of the extremity, with thickening of the distal phalange and longitudinal striationsthe distal phalange and longitudinal striations on the fingernail.on the fingernail.
  • 12. Clinical HistoryClinical History  The development of clubbing usually is gradual enoughThe development of clubbing usually is gradual enough that many patients are unaware of its presence;that many patients are unaware of its presence; however, some patients may report swelling of the distalhowever, some patients may report swelling of the distal portion of the digits, which may be bilateral or unilateralportion of the digits, which may be bilateral or unilateral or may involve a single digit.or may involve a single digit.  Although clubbing typically is painless, it rarely mayAlthough clubbing typically is painless, it rarely may present with pain in the fingertips.present with pain in the fingertips.  Rapid postoperative resolution of clubbing in a few daysRapid postoperative resolution of clubbing in a few days was described in a patient with aortic and mitral valvewas described in a patient with aortic and mitral valve replacement due to infective endocarditisreplacement due to infective endocarditis..
  • 13. EvaluationEvaluation  Ask the history aboutAsk the history about  Respiratory symptomsRespiratory symptoms  Cardiovascular symptomsCardiovascular symptoms  Gastrointestinal symptomsGastrointestinal symptoms  Non specific symptoms such as evening riseNon specific symptoms such as evening rise temp. anorexia ,wt losstemp. anorexia ,wt loss  Smoking, alcohol intake, exposure to toxicSmoking, alcohol intake, exposure to toxic substancessubstances
  • 14. ExaminationExamination  To examine for finger clubbing, first look across the nailTo examine for finger clubbing, first look across the nail and nail bed at the 'nail bed angle'. This is normallyand nail bed at the 'nail bed angle'. This is normally obtuse but can not be seen in the early stages of fingerobtuse but can not be seen in the early stages of finger clubbing.clubbing.  To detect nail bed fluctuation place both thumbs underTo detect nail bed fluctuation place both thumbs under the pulp of the terminal phalanx and attempt to move thethe pulp of the terminal phalanx and attempt to move the nail within the nail bed using your index fingers. Anail within the nail bed using your index fingers. A 'spongy feel' confirms nail bed fluctuation.'spongy feel' confirms nail bed fluctuation.  The sponginess results from increased fibrovascularThe sponginess results from increased fibrovascular tissue between the nail and the phalanx.tissue between the nail and the phalanx.
  • 15. Physical findingPhysical finding  Two objective measures for determining theTwo objective measures for determining the presence of clubbing have been proposedpresence of clubbing have been proposed  1. Digital index 2. DPD/IPD1. Digital index 2. DPD/IPD 1.1. Digital indexDigital index measures 2 separate circumferences on eachmeasures 2 separate circumferences on each of the 10 fingers at the nail bed (NB) and theof the 10 fingers at the nail bed (NB) and the distal interphalangeal joint (DIP). The sum ofdistal interphalangeal joint (DIP). The sum of the 10 ratios (NB:DIP) determines digital indexthe 10 ratios (NB:DIP) determines digital index If it is more than 10, it signifies the clubbing.If it is more than 10, it signifies the clubbing.
  • 16. 22 Another method to detectAnother method to detect clubbing is measurementclubbing is measurement of the phalangeal depthof the phalangeal depth ratio ( DPD/IPD )ratio ( DPD/IPD )  In a normal finger it is <1,In a normal finger it is <1, the distal phalangealthe distal phalangeal depth is smaller than thedepth is smaller than the interphalangeal depth.interphalangeal depth.  In clubbing thisIn clubbing this relationship is reversedrelationship is reversed (>1).(>1).  The measurement canThe measurement can easily be taken using aeasily be taken using a calipercaliper
  • 17. Profile signProfile sign  The degree of the deformity may be measured byThe degree of the deformity may be measured by Lovibond’s ‘profile sign’ which measures the angleLovibond’s ‘profile sign’ which measures the angle between the curved nail plate and the proximal nail foldbetween the curved nail plate and the proximal nail fold  This is normally 160°, but exceeds 180° in clubbing.This is normally 160°, but exceeds 180° in clubbing.  A modified profile sign is assessed by measuring theA modified profile sign is assessed by measuring the angle between the middle and the terminal phalanx atangle between the middle and the terminal phalanx at the interphalangeal joint: in normal fingers the distalthe interphalangeal joint: in normal fingers the distal phalanx forms an almost straight (180°) extension of thephalanx forms an almost straight (180°) extension of the middle phalanx, whereas in severe clubbing this anglemiddle phalanx, whereas in severe clubbing this angle may be reduced to160° or even 140°.may be reduced to160° or even 140°.
  • 18. Schamroth’s signSchamroth’s sign  The best indicator may beThe best indicator may be the simple clinical methodthe simple clinical method adopted by Schamroth:adopted by Schamroth:  In normal individuals aIn normal individuals a distinct aperture ordistinct aperture or schamroth’s window,schamroth’s window, usually diamond-shaped,usually diamond-shaped, is formed at the base ofis formed at the base of the nail bed when twothe nail bed when two fingers held together withfingers held together with nails facing each other.nails facing each other.  Early clubbing obliteratesEarly clubbing obliterates this window.this window.
  • 19.  INTERESTIG thing is that Schamroth not onlyINTERESTIG thing is that Schamroth not only described the sign but himself was the patient.described the sign but himself was the patient.  In a report published back in 1976 ,he describedIn a report published back in 1976 ,he described not only his 3 attacks of infective endocarditisnot only his 3 attacks of infective endocarditis ,but also the clinical sign that bears his name.,but also the clinical sign that bears his name. “Schamroth’ sign.”“Schamroth’ sign.”
  • 20. CLASSIFICATIONCLASSIFICATION NormalNormal MildMild ModerateModerate SevereSevere DPD/IPDDPD/IPD <1<1 >1>1 >1>1 >1>1 Profile AngleProfile Angle <160<160 <180<180 =180=180 >180>180 Fishman classified clubbing in to following category by using ratio of distal phalangeal distance &inter phalangeal distance & Profile angle that is angle between nail bed and nail
  • 21. PathophisiologyPathophisiology  The specific pathophysiologic mechanism ofThe specific pathophysiologic mechanism of digital clubbing remains unknown. Many theoriesdigital clubbing remains unknown. Many theories have been proposed, yet none have receivedhave been proposed, yet none have received widespread acceptance as a comprehensivewidespread acceptance as a comprehensive explanation for the phenomenon of digitalexplanation for the phenomenon of digital clubbing.clubbing.  As stated best by Samuel West in 1897,As stated best by Samuel West in 1897, "Clubbing is one of those phenomena with which"Clubbing is one of those phenomena with which we are all so familiar that we appear to knowwe are all so familiar that we appear to know more about it than we really do."more about it than we really do."
  • 22.  Theories suggested for theTheories suggested for the pathogenesis of Hypertrophicpathogenesis of Hypertrophic osteoarthropathy & clubbingosteoarthropathy & clubbing 1.1. NeurogenicNeurogenic 2.2. HumoralHumoral 3.3. Role of megakaryocytes and largeRole of megakaryocytes and large platelet particlesplatelet particles 4.4. Genetic & familialGenetic & familial 5.5. HypoxiaHypoxia
  • 23. NEUROGENICNEUROGENIC  Based on the observation that vagotomyBased on the observation that vagotomy resulted in symptomatic improvement in theresulted in symptomatic improvement in the small number of pt of lung tumors & HOA,small number of pt of lung tumors & HOA,  It was postulated that afferent vagal stimuli fromIt was postulated that afferent vagal stimuli from the tumor site led via intercostal nerves / vagi tothe tumor site led via intercostal nerves / vagi to brainstem from where efferent nerve impulsesbrainstem from where efferent nerve impulses to terminal /distal extremities causingto terminal /distal extremities causing vasodilatation and resulting in changes thatvasodilatation and resulting in changes that leads to HOA.leads to HOA.  But this theory cant explain the clubbing inBut this theory cant explain the clubbing in condition where vagal stimulation not occurs.condition where vagal stimulation not occurs.
  • 24. HUMORALHUMORAL  Humoral theory postulated that solubleHumoral theory postulated that soluble substances that’s are normally inactivated orsubstances that’s are normally inactivated or removed during passage through the lungremoved during passage through the lung reached the systemic circulation in an activereached the systemic circulation in an active form and stimulated the changes of HOA .( pg,form and stimulated the changes of HOA .( pg, bradykinin, estrogen, ferritin, gh)bradykinin, estrogen, ferritin, gh)  But it is found that the level of such substancesBut it is found that the level of such substances in serum does not differ from normal individual.in serum does not differ from normal individual.
  • 25. Megakaryocytes + large platelet particle Bypass lung Reach distal extremities Interact with endothelial cells Release of PDGF Stimulation of fibroblast TGF-β Proliferation of connective tissues & Periostium SHUNT THEORYSHUNT THEORY
  • 26. GENETICGENETIC  A mutation in theA mutation in the HPGDHPGD gene encodinggene encoding nicotinamide (NAD)+ –dependent 15-nicotinamide (NAD)+ –dependent 15- hydroxyprostaglandin dehydrogenasehydroxyprostaglandin dehydrogenase was identified in a largewas identified in a large Pakistani family with isolated congenital nail clubbing.Pakistani family with isolated congenital nail clubbing.  Clubbing is a feature of Pachydermoperiostosis (PDP), aClubbing is a feature of Pachydermoperiostosis (PDP), a rare genodermatosis usually an autosomal dominantrare genodermatosis usually an autosomal dominant model with incomplete penetrance and variablemodel with incomplete penetrance and variable expression, but also both autosomal recessive and X-expression, but also both autosomal recessive and X- linked inheritance have been suggested in some PDPlinked inheritance have been suggested in some PDP families.families.
  • 27. HPGD & PGE2HPGD & PGE2  Importantly, 15-hydroxyprostaglandinImportantly, 15-hydroxyprostaglandin dehydrogenase is the main enzyme responsibledehydrogenase is the main enzyme responsible for breaking down offor breaking down of prostaglandin E2prostaglandin E2 (PGE2, a lipid compound which has a number of(PGE2, a lipid compound which has a number of functions in the lung, the GI tract, and in thefunctions in the lung, the GI tract, and in the uterus during pregnancy) and otheruterus during pregnancy) and other prostaglandins and related compounds.prostaglandins and related compounds.  Gene responsible for HPGD is located onGene responsible for HPGD is located on chromosome 4 q34chromosome 4 q34
  • 28.  HPGD, the key enzyme in prostaglandin degradation,HPGD, the key enzyme in prostaglandin degradation, PGE2 is known to have a number of effects upon bone.PGE2 is known to have a number of effects upon bone.  Mutations in the key enzyme of prostaglandinMutations in the key enzyme of prostaglandin degradation lead to PHO, suggests that elevateddegradation lead to PHO, suggests that elevated prostaglandin levels are critical in causing the muchprostaglandin levels are critical in causing the much more common clubbing seen in pulmonary hypertrophicmore common clubbing seen in pulmonary hypertrophic osteoarthropathyosteoarthropathy  As the lung is known to be a site of PGE2 clearance byAs the lung is known to be a site of PGE2 clearance by HPGD, perhaps the lung diseases associated withHPGD, perhaps the lung diseases associated with pulmonary hypertrophic osteoarthropathy lead topulmonary hypertrophic osteoarthropathy lead to decreased clearance and degradation of PGE2.decreased clearance and degradation of PGE2.  This association also seen in PDA.This association also seen in PDA.
  • 29.  Structural model of PGE2Structural model of PGE2 bound to HPGD (Colinbound to HPGD (Colin Fishwick, School ofFishwick, School of Chemistry, Leeds),Chemistry, Leeds), showing the predictedshowing the predicted effect of the PHOeffect of the PHO mutation A140P,mutation A140P, displacing the substratedisplacing the substrate and preventingand preventing coordination of its 15-OHcoordination of its 15-OH group to serine 138.group to serine 138.
  • 30. HYPOXYAHYPOXYA  Hypoxia has been proposed as an alternativeHypoxia has been proposed as an alternative explanation for clubbing in cyanotic heartexplanation for clubbing in cyanotic heart disease and pulmonary diseases.disease and pulmonary diseases.  An increase in hypoxia may activate localAn increase in hypoxia may activate local vasodilators, consequently increasing blood flowvasodilators, consequently increasing blood flow to the distal portion of the digits that leads toto the distal portion of the digits that leads to hypertrophy of fibroconective tissue of nail bed.hypertrophy of fibroconective tissue of nail bed.  However, in most cases, hypoxia is absent in theHowever, in most cases, hypoxia is absent in the presence of clubbing, and many diseases withpresence of clubbing, and many diseases with noted hypoxia are not associated with clubbingnoted hypoxia are not associated with clubbing
  • 31.  There are three main types of clubbing:There are three main types of clubbing:  1 Simple clubbing.1 Simple clubbing.  2 Hypertrophic pulmonary osteoarthropathy.2 Hypertrophic pulmonary osteoarthropathy.  3 Pachydermoperiostosis.3 Pachydermoperiostosis.
  • 32. Simple clubbingSimple clubbing  characteristics:characteristics:  Increased nail curvature occurs with a transverse furrowIncreased nail curvature occurs with a transverse furrow separating it from the rest of the nail both in the early stageseparating it from the rest of the nail both in the early stage and after resolution. The onset is usually gradual andand after resolution. The onset is usually gradual and painless,painless, except in some cases of carcinoma of the lung in which clubbingexcept in some cases of carcinoma of the lung in which clubbing may develop abruptly and be associated with severe painmay develop abruptly and be associated with severe pain..  Hypertrophy of the soft parts of the terminal segment causedHypertrophy of the soft parts of the terminal segment caused by firm, elastic, oedematous infiltration of the pulp, whichby firm, elastic, oedematous infiltration of the pulp, which may spread to the dorsal surface with marked periungualmay spread to the dorsal surface with marked periungual swelling.swelling.  Hyperplasia of the dermal fibro vascular tissue may extendHyperplasia of the dermal fibro vascular tissue may extend to involve the adjacent matrix.to involve the adjacent matrix. This accounts for one of the earliestThis accounts for one of the earliest signs of clubbing—abnormal mobility of the nail base, which can be rocked backsigns of clubbing—abnormal mobility of the nail base, which can be rocked back and forth giving the impression that it is floating on a soft oedematous padand forth giving the impression that it is floating on a soft oedematous pad..  Acral cyanosis is often observedAcral cyanosis is often observed
  • 33. Hypertrophic pulmonary osteoarthropathyHypertrophic pulmonary osteoarthropathy  Clubbing of the nails.Clubbing of the nails.  Hypertrophy of the upper and lower extremitiesHypertrophy of the upper and lower extremities  Joint changes with pseudo-inflammatory, symmetrical,Joint changes with pseudo-inflammatory, symmetrical, painful arthropathy of the large joints, especially thosepainful arthropathy of the large joints, especially those of the legs.of the legs. This syndrome is almost pathognomonic of lung carcinoma andThis syndrome is almost pathognomonic of lung carcinoma and mesothelioma of the pleura; less commonly bronchiectasis . Along with thismesothelioma of the pleura; less commonly bronchiectasis . Along with this Gynaecomastia may also be present.Gynaecomastia may also be present.  There may bilateral, proliferative periostitis andThere may bilateral, proliferative periostitis and moderate, diffuse decalcification of bone.moderate, diffuse decalcification of bone.  Peripheral neurovascular disorders such as localPeripheral neurovascular disorders such as local cyanosis and paraesthesia are not uncommoncyanosis and paraesthesia are not uncommon
  • 34. PachydermoperiostosisPachydermoperiostosis (( primary hypertrophic osteoarthropathy )primary hypertrophic osteoarthropathy )  The digital changes typically begin at or about the time ofThe digital changes typically begin at or about the time of puberty.puberty.  Autosomal dominant trait, nine times more common in boysAutosomal dominant trait, nine times more common in boys than girls.than girls.  The ends of the fingers and toes are bulbous and often clubThe ends of the fingers and toes are bulbous and often club shaped, with hyperhidrosis of the hands and the feetshaped, with hyperhidrosis of the hands and the feet  The clubbing stops abruptly at the distal interphalangeal joint.The clubbing stops abruptly at the distal interphalangeal joint. the finger tips are clinically identical to those of hypertrophic pulmonarythe finger tips are clinically identical to those of hypertrophic pulmonary osteoarthropathy.osteoarthropathy.  However, in Pachydermoperiostosis the thickened cortexHowever, in Pachydermoperiostosis the thickened cortex appears homogeneous on X-ray examination and does notappears homogeneous on X-ray examination and does not impinge on the medullary spaceimpinge on the medullary space..
  • 35.  Acro-osteolysis of theAcro-osteolysis of the distal phalanges hasdistal phalanges has been reported.been reported.  The pachydermal changeThe pachydermal change of the extremities andof the extremities and face, with furrowing onface, with furrowing on forehead and greasy skin,forehead and greasy skin, cutis verticis gyrata is thecutis verticis gyrata is the most characteristicmost characteristic feature of the disorder; itfeature of the disorder; it is termed the Touraine-is termed the Touraine- Solente-Golé syndrome.Solente-Golé syndrome.
  • 37. THYROID ACROPACHYTHYROID ACROPACHY  Hyperthyroidism graves disease treated or untreatedHyperthyroidism graves disease treated or untreated occasionally associated with clubbing & periostitis ofoccasionally associated with clubbing & periostitis of the bones of the feet & hands. This condition knownthe bones of the feet & hands. This condition known as thyroid acropachyas thyroid acropachy  Periostitis is asymptomatic, occurs at midshaft & diaphysealPeriostitis is asymptomatic, occurs at midshaft & diaphyseal portion of metacarpals & phalangeal bones.portion of metacarpals & phalangeal bones.  Elevated levels of long acting thyroid stimulator are found inElevated levels of long acting thyroid stimulator are found in the serum of these patients.the serum of these patients.
  • 39. CausesCauses  Idiopathic or primary clubbingIdiopathic or primary clubbing  Pachydermoperiostisis Clubbing is seen inPachydermoperiostisis Clubbing is seen in 89% cases of PDP,89% cases of PDP,  familial clubbing,familial clubbing,  Secondary hypertrophic osteoarthropathySecondary hypertrophic osteoarthropathy
  • 40. Causes of secondary clubbingCauses of secondary clubbing include the following :include the following :  Pulmonary disease – 80%Pulmonary disease – 80%  Lung cancer,Lung cancer,  cystic fibrosis,cystic fibrosis,  interstitial lung disease,interstitial lung disease,  idiopathic pulmonary fibrosis,idiopathic pulmonary fibrosis,  sarcoidosis,sarcoidosis,  Bronchiectasis , empyema,Bronchiectasis , empyema,  TuberculosisTuberculosis  Pleural mesothelioma, pulmonary artery sarcoma,Pleural mesothelioma, pulmonary artery sarcoma, cryptogenic fibrosing alveolitis, and pulmonarycryptogenic fibrosing alveolitis, and pulmonary metastasesmetastases
  • 41.  Cardiac disease –Cardiac disease –  Cyanotic congenital heart disease,Cyanotic congenital heart disease,  other causes of right-to-left shunting,other causes of right-to-left shunting,  and bacterial endocarditisand bacterial endocarditis
  • 42.  Gastrointestinal disease –Gastrointestinal disease –  Ulcerative colitis,Ulcerative colitis,  Crohn's disease 38%,Crohn's disease 38%,  Primary biliary cirrhosis,Primary biliary cirrhosis,  Cirrhosis of the liver,Cirrhosis of the liver,  Leiomyoma of the esophagus, achalasia,Leiomyoma of the esophagus, achalasia,  And peptic ulceration of the esophagusAnd peptic ulceration of the esophagus
  • 43.  Malignancies –Malignancies –  Thyroid cancer,Thyroid cancer,  Thymus cancer,Thymus cancer,  Hodgkin disease,Hodgkin disease,  Disseminated chronic myeloid leukemiaDisseminated chronic myeloid leukemia  POEMSPOEMS  [polyneuropathy, organomegaly, endocrinopathy,[polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes]monoclonal gammopathy, and skin changes]
  • 44.  POEMSPOEMS  [[polyneuropathy, organomegaly, endocrinopathy, monoclonalpolyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changesgammopathy, and skin changes] syndrome is a rare] syndrome is a rare paraneoplastic syndrome secondary to a plasma cellparaneoplastic syndrome secondary to a plasma cell dyscrasia in which clubbing may be seen.dyscrasia in which clubbing may be seen.  Other findings including peripheral neuropathy,Other findings including peripheral neuropathy, organomegaly, endocrinopathy, monoclonalorganomegaly, endocrinopathy, monoclonal plasma proliferative disorder, skin changes,plasma proliferative disorder, skin changes, sclerotic bone lesions, Castleman disease,sclerotic bone lesions, Castleman disease, thrombocytosis, papilledema, peripheral edema,thrombocytosis, papilledema, peripheral edema, pleural effusions, ascites, and white nailpleural effusions, ascites, and white nail
  • 45.  Miscellaneous conditions –Miscellaneous conditions –  Acromegaly,Acromegaly,  Thyroid acropachy,Thyroid acropachy,  Pregnancy ,Pregnancy ,  An unusual complication of severe secondaryAn unusual complication of severe secondary hyperparathyroidism,hyperparathyroidism,  Hypoxemia possibly related to long-termHypoxemia possibly related to long-term smoking of cannabissmoking of cannabis  Occupational acro-osteolysis (exposure toOccupational acro-osteolysis (exposure to vinyl chloride).vinyl chloride).
  • 47.  Clubbing in toes seen in infected abdominal aneurismClubbing in toes seen in infected abdominal aneurism
  • 48. (1) Psuedoclubbing in trauma (2) in case of Acromegaly (3) clubbing Hook nail deformity
  • 49. Psuedoclubing in yellow nail syndrome
  • 50. Histological FindingsHistological Findings  Microscopically,Microscopically,  The collagen fibrils and cells are separated by aThe collagen fibrils and cells are separated by a distance greater than that seen in histologicallydistance greater than that seen in histologically normal specimens. This increased separation resultsnormal specimens. This increased separation results in a less dense nail bed matrixin a less dense nail bed matrix  Primitive fibroblasts are seen with large nuclei,Primitive fibroblasts are seen with large nuclei, basophilic cytoplasm, and long reticular processes.basophilic cytoplasm, and long reticular processes.  Increased and scattered extra vascular lymphocytesIncreased and scattered extra vascular lymphocytes and, less often, a moderately increased number ofand, less often, a moderately increased number of tissue eosinophils also are noted in the nail beds oftissue eosinophils also are noted in the nail beds of some specimens.some specimens.  The Periostium of the nail bed may be thickened withThe Periostium of the nail bed may be thickened with increased vascular penetration.increased vascular penetration.
  • 51.  Eventually, increased collagen is laid down in allEventually, increased collagen is laid down in all types of chronic clubbing. The mat of collagen fiberstypes of chronic clubbing. The mat of collagen fibers may be abnormally thick and dense. The walls of themay be abnormally thick and dense. The walls of the vascular components increase in thickness and arevascular components increase in thickness and are encased in a thick fibrous sheet. At this stage ofencased in a thick fibrous sheet. At this stage of clubbing, the histologic and morphologic changesclubbing, the histologic and morphologic changes probably are irreversibleprobably are irreversible
  • 52. INVESTIGATIONINVESTIGATION  Laboratory StudiesLaboratory Studies  Because clubbing typically is secondary to anBecause clubbing typically is secondary to an underlying pathological process, performunderlying pathological process, perform pertinent laboratory studies for primarypertinent laboratory studies for primary medical disorders that are suggested clinicallymedical disorders that are suggested clinically
  • 53.  Imaging StudiesImaging Studies  Radiographic studies include bone dissolution, bone formation,Radiographic studies include bone dissolution, bone formation, or no change in the bone of the distal phalanx.or no change in the bone of the distal phalanx.  The types of changes may depend on the underlyingThe types of changes may depend on the underlying pathological processes, as well as the duration of the processes.pathological processes, as well as the duration of the processes.  The lysis of bone predominates in the digits of patients withThe lysis of bone predominates in the digits of patients with congenital cyanotic heart disease, while hypertrophycongenital cyanotic heart disease, while hypertrophy predominates in the digits of patients with clubbing secondary topredominates in the digits of patients with clubbing secondary to pulmonary conditions.pulmonary conditions.  As an alternate view, hypertrophy may occur earlier in theAs an alternate view, hypertrophy may occur earlier in the process of clubbing, and, eventually, it may change to osteolysisprocess of clubbing, and, eventually, it may change to osteolysis as the process becomes chronic.as the process becomes chronic.
  • 54.  Radiograph of both handsRadiograph of both hands in a 42-year-old man within a 42-year-old man with a family history ofa family history of primary hypertrophicprimary hypertrophic osteoarthropathy who hadosteoarthropathy who had coarsened facial featurescoarsened facial features and thickness of the scalp.and thickness of the scalp.  Note the soft tissueNote the soft tissue clubbing and acro-clubbing and acro- osteolysis of the terminalosteolysis of the terminal phalanges.phalanges.
  • 55. Radiograph showing thickened, columnarRadiograph showing thickened, columnar diaphyses and erosion of the terminaldiaphyses and erosion of the terminal phalangeal tufts in PHOphalangeal tufts in PHO..
  • 56.  Technetium Tc 99m skeletal imagingTechnetium Tc 99m skeletal imaging  may be helpful in determining the presencemay be helpful in determining the presence and extent of bone changes in clubbed digits,and extent of bone changes in clubbed digits, which show increased uptake of thewhich show increased uptake of the radionuclide.radionuclide.  The increased, intense, symmetric uptakeThe increased, intense, symmetric uptake typically is localized to the nail beds and maytypically is localized to the nail beds and may result from increased blood flow and changesresult from increased blood flow and changes in the surrounding soft tissuesin the surrounding soft tissues
  • 57.  Radionuclide scansRadionuclide scans show the typicalshow the typical appearance ofappearance of secondarysecondary hypertrophichypertrophic osteoarthropathyosteoarthropathy caused by acaused by a bronchogenicbronchogenic carcinoma.carcinoma.
  • 58.  ThermographyThermography  It is another imaging modality being studiedIt is another imaging modality being studied for use in diagnosis and monitoring of patientsfor use in diagnosis and monitoring of patients with digital clubbing.with digital clubbing.  Patients may show increased temperature inPatients may show increased temperature in the distal digits, which can be attributed to anthe distal digits, which can be attributed to an increase in blood flow secondary toincrease in blood flow secondary to vasodilation.vasodilation.  Not all patients with clubbing have positiveNot all patients with clubbing have positive thermographic resultsthermographic results
  • 59.  Positron emission tomographyPositron emission tomography  It also has been used to study the glucose metabolism ofIt also has been used to study the glucose metabolism of clubbed digits. An increased signal, indicating increased glucoseclubbed digits. An increased signal, indicating increased glucose metabolism, has been demonstrated in the distal part of themetabolism, has been demonstrated in the distal part of the clubbed fingers. These changes are not seen in fingertips withclubbed fingers. These changes are not seen in fingertips with normal morphology. The increase in signal supports the theorynormal morphology. The increase in signal supports the theory that clubbing is caused by the presence of a factor (eg, platelet-that clubbing is caused by the presence of a factor (eg, platelet- derived growth factor) that increases cellular metabolism.derived growth factor) that increases cellular metabolism.  Other imaging studies, such as computed tomography orOther imaging studies, such as computed tomography or magnetic resonance imaging, may be helpful inmagnetic resonance imaging, may be helpful in evaluating the patient for the primary pathologicalevaluating the patient for the primary pathological process causing the clubbing.process causing the clubbing.
  • 60. TreatmentTreatment  Medical CareMedical Care  No specific treatment for clubbing is available.No specific treatment for clubbing is available. Treatment of the underlying pathologicalTreatment of the underlying pathological condition may decrease the clubbing or,condition may decrease the clubbing or, potentially, reverse it if performed earlypotentially, reverse it if performed early enough. Once substantial chronic tissueenough. Once substantial chronic tissue changes, including increased collagenchanges, including increased collagen deposition, have occurred, reversal is unlikely.deposition, have occurred, reversal is unlikely.  Treatment for related problems, such as pain,Treatment for related problems, such as pain, is symptomatic.is symptomatic.
  • 61.  Surgical CareSurgical Care  No specific surgical procedures are performedNo specific surgical procedures are performed for clubbing. Appropriate surgical treatment offor clubbing. Appropriate surgical treatment of underlying disease, such as tumor removal inunderlying disease, such as tumor removal in patients with lung cancer, may improve orpatients with lung cancer, may improve or reverse clubbing, provided that permanentreverse clubbing, provided that permanent morphologic changes have not occurredmorphologic changes have not occurred..
  • 62.  Medico legal PitfallsMedico legal Pitfalls  Failure to perform a thorough and exhaustiveFailure to perform a thorough and exhaustive workup of the patient who presents withworkup of the patient who presents with clubbing of the nails since clubbing is aclubbing of the nails since clubbing is a physical finding associated with many severephysical finding associated with many severe disease processes, including severaldisease processes, including several malignanciesmalignancies
  • 63.  ReferencesReferences  Harrison's principals of internal medicine,Harrison's principals of internal medicine,  Hutchison’s clinical methodsHutchison’s clinical methods  Macleod's clinical methodMacleod's clinical method  Crofton & Douglus Respiratory diseasesCrofton & Douglus Respiratory diseases  P J Mehta’s practical medicineP J Mehta’s practical medicine  British medical journalBritish medical journal  Internet emedicine.comInternet emedicine.com  Goyal S, Griffiths AD, Omarouayache S, Mohammedi R. An improved method of studying fingernailGoyal S, Griffiths AD, Omarouayache S, Mohammedi R. An improved method of studying fingernail morphometry: application to the early detection of fingernail clubbing.morphometry: application to the early detection of fingernail clubbing. J Am AcadJ Am Acad DermatolDermatol. Oct 1998;39(4 Pt 1):640-2.. Oct 1998;39(4 Pt 1):640-2.  Castori M, Sinibaldi L, Mingarelli R, Lachman RS, Rimoin DL, DallapiccolaCastori M, Sinibaldi L, Mingarelli R, Lachman RS, Rimoin DL, Dallapiccola B. Pachydermoperiostosis: an update.B. Pachydermoperiostosis: an update. Clin GenetClin Genet. Dec 2005;68(6):477-86.. Dec 2005;68(6):477-86.  Tariq M, Azeem Z, Ali G, Chishti MS, Ahmad W. Mutation in the HPGD gene encoding NAD+Tariq M, Azeem Z, Ali G, Chishti MS, Ahmad W. Mutation in the HPGD gene encoding NAD+ dependent 15-hydroxyprostaglandin dehydrogenase underlies isolated congenital nail clubbingdependent 15-hydroxyprostaglandin dehydrogenase underlies isolated congenital nail clubbing (ICNC).(ICNC). J Med GenetJ Med Genet. Jan 2009;46(1):14-20.. Jan 2009;46(1):14-20.  Dickinson CJ, Martin JF. Megakaryocytes and platelet clumps as the cause of fingerDickinson CJ, Martin JF. Megakaryocytes and platelet clumps as the cause of finger clubbing.clubbing. LancetLancet. Dec 19 1987;2(8573):1434-5.. Dec 19 1987;2(8573):1434-5.  Ddungu H, Johnson JL, Smieja M, Mayanja-Kizza H. Digital clubbing in tuberculosis--relationshipDdungu H, Johnson JL, Smieja M, Mayanja-Kizza H. Digital clubbing in tuberculosis--relationship to HIV infection, extent of disease and hypoalbuminemia.to HIV infection, extent of disease and hypoalbuminemia. BMC Infect DisBMC Infect Dis. Mar 10 2006;6:45.. Mar 10 2006;6:45.