Prospective study of periostitis and finger clubbing in primary biliary cirrhosis and other forms of chronic liver disease.
ABSTRACT The association of finger clubbing and periostitis has been reported in primary biliary cirrhosis and, more rarely, in other forms of chronic liver disease. The prevalence of periostitis and its relationship to finger clubbing is unknown. In this prospective study, we have determined the prevalence of periostitis and finger clubbing in 74 patients with primary biliary cirrhosis and 54 with other forms of chronic liver disease. Clubbing was present in 24% of patients with primary biliary cirrhosis, 29% with HBsAg negative chronic active hepatitis, and 23% in the group of miscellaneous liver diseases. Symmetrical periostitis affecting the tibiae and fibulae occurred in 35% of patients with primary biliary cirrhosis, 29% with chronic, active hepatitis and 40% of patients in the miscellaneous group. The distal radii and ulnae were affected in only eight patients (6%). In primary biliary cirrhosis, the presence of finger clubbing was strongly associated with periostitis (P less than 0.01), but this association was uncommon in other forms of chronic liver disease. In all forms of chronic liver disease periostitis commonly occurs in the absence of finger clubbing. Marked tenderness over the distal leg bones is a reliable sign of underlying periostitis, but this sign is present in only a third of affected patients. This study indicates that periostitis affecting the lower leg bones is common in patients with chronic liver disease, and its presence should be sought whether or not the patient has finger clubbing.
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Article: Digital clubbing.[Show abstract] [Hide abstract]
ABSTRACT: Digital clubbing is an ancient and important clinical signs in medicine. Although clubbed fingers are mostly asymptomatic, it often predicts the presence of some dreaded underlying diseases. Its exact pathogenesis is not known, but platelet-derived growth factor and vascular endothelial growth factor are recently incriminated in its causation. The association of digital clubbing with various disease processes and its clinical implications are discussed in this review.Lung India 10/2012; 29(4):354-62.
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ABSTRACT: Background: Cardiovascular abnormalities are among common complication in patients with cirrhosis waiting for liver transplantation (LT). The aim of the present study was to investigate cardiac abnormalities among pediatric liver transplant candidates.Methods: We prospectively evaluated the pediatric patient aged less than 18 years listed for LT between 2006 and 2008. Besides history taking and physical examination all the patients underwent electrocardiogram, chest radiograph, contrast echocardiography and color Doppler echocardiography, as well as arterial blood gas analyses.Results: Totally 89 patients with mean age of 8.1±4.6 years were included in the study. The most common causes for liver disease were cryptogenic cirrhosis followed by biliary atresia and autoimmune cirrhosis. Clubbing was found in 27 out of 89 patients and was the most common abnormalities in physical examination. In 22 patients (24.7%) heart murmur was heard by a pediatric cardiologist. Sixty nine patients (77.5%) had normal cardiac findings in chest radiograph. Cardiomegaly was found in 17 (19.1%) patients as the most common abnormal finding in chest radiograph. Electrocardiogram showed sinus tachycardia in 16 (18%) patients. Eleven patients (12.4%) had tricuspid regurgitation as the most common abnormal findings in echocardiography. Thirteen (14.6%) patients had positive contrast echocardiography in favor of intrapulmonary shunt.Conclusion: As the leading cause of post transplant death after graft rejection are cardiovascular complications cardiac evaluation should be considered in all pediatric patients before LT to lower morbidity and mortality during and after transplantation.Journal of Pediatric Sciences. 01/2010;
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ABSTRACT: Primary intestinal lymphangiectasia (PIL), also known as Waldmann's disease, is a rare disorder characterized by dilated intestinal lacteals resulting in lymph leakage into the small bowel lumen and responsible for protein-losing enteropathy leading to lymphopenia, hypoalbuminemia and hypogammaglobulinemia. The symptoms usually start in early infancy. We report a case of secondary hyperparathyroidism, osteopenia, monoclonal gammopathy and digital clubbing in a 57-year-old patient with a 12-year history of discontinuous diarrhea. Malabsorption with inability to gain weight, and finally weight loss and formation of leg edema were associated with protein-losing enteropathy. A low-fat diet associated with medium-chain triglyceride supplementation was clinically effective as medical management in reducing diarrhea and leg edema, and promoting weight gain. Double-balloon enteroscopy and small bowel biopsy histopathology confirmed dilated intestinal lacteals. Digital clubbing associated with primary intestinal lymphangiectasia which may causally be related to chronic platelet excess has not been reported before.Wiener Medizinische Wochenschrift 08/2010; 160(15-16):431-6.
Gut, 1981, 22, 203-206
Prospective study of periostitis and finger clubbing in
primary biliary cirrhosis and other forms of chronic
0 EPSTEIN, R DICK, AND S SHERLOCK
From the Academic Department ofMedicine and Department ofRadiology, Royal Free Hospital, London
cirrhosis and, more rarely, in other forms of chronic liver disease. The prevalence of periostitis and
its relationship to finger clubbing is unknown. In this prospective study, we have determined the
prevalence of periostitis and finger clubbing in 74 patients with primary biliary cirrhosis and 54 with
other forms of chronic liver disease. Clubbing was present in 24% of patients with primary biliary
cirrhosis, 29% with HBsAg negative chronic active hepatitis, and 23 % in the group ofmiscellaneous
liver diseases. Symmetrical periostitis affecting the tibiae and fibulae occurred in 35% of patients
with primary biliary cirrhosis, 29% with chronic, active hepatitis and 40% of patients in the miscel-
laneous group. The distal radii and ulnae were affected in only eight patients (6%). In primary
biliary cirrhosis, the presence of finger clubbing was strongly associated with periostitis (p < 0.01).
but this association was uncommon in other forms of chronic liver disease. In all forms of chronic
liver disease periostitis commonly occurs in the absence of finger clubbing. Marked tenderness over
-the distal leg bones is a reliable sign of underlying periostitis, but this sign is present in only a third
of affected patients. This study indicates that periostitis affecting the lower leg bones is common in
patients with chronic liver disease, and its presence should be sought whether or not the patient has
The association of finger clubbing and periostitis has been reported in primary biliary
Finger clubbing is a well-recognised sign of chronic
liver disease, especially primary biliary cirrhosis
(PBC) and chronic active hepatitis (CAH).' The
association offinger clubbing and periostitis has been
reported in PBC, and, more rarely, in other forms of
,chronic liver disease, and the syndrome of hyper-
trophic hepatic osteoarthropathy should be con-
sidered in the differential diagnosis of bone and
joint pain in patients with chronic liver disease.2
The prevalence of periostitis in PBC and other
forms of chronic liver disease is unknown. It has been
patients with finger clubbing and skeletal symptoms,2
but this assumes that periostitis occurs only in the
presence of finger clubbing. The aim of this pros-
pective study was to determine the prevalence of
periostitis in PBC and other forms of chronic liver
disease, and to define the relationship between
periostitis and finger clubbing.
should be sought
Received for publication 30 September 1980.
One hundred and twenty-eight consecutive patients
with biopsy-proven chronic liver disease have been
studied, including 74 with PBC, and 54 with other
forms of chronic liver disease (Table 1). All the
patients were attending routine outpatient clinics,
and possible intrathoracic causes of clubbing and
periostitis were excluded by routine chest radiology.
Skeletal symptoms (bone and joint pain) and signs
(bone tenderness and arthritis) were recorded and
finger clubbing was judged to be present when
obvious loss of the angle between the nail and the
nail bed was associated with sponginess of the nail
bed.3 When the clinical evaluation of clubbing was
equivocal, the angle between the nail and nail bed
was measured using a shadowgraph similar to that
described by Bentley et al.4 (Fig. 1). To establish a
normal range for the nail-nail bed angle, this angle
was measured in 75 healthy controls, and clubbing
was diagnosed when the nail-nail bed angle was
1-65 standard deviations from the
204Epstein, Dick, and Sherlock
Table 1Patients studied, sex, mean age, and age range (years), and diseases included in mixed group
Primary biliary cirrhosis
Chronic active hepatitis
Mixed liver diseases (MLD)
2' biliary cirrhosis
normal (95% confidence limit using a one-sided
In liver disease, periostitis first affects the distal
tibiae and fibulae and,
affected patients can be detected by performing an
anteroposterior radiograph of the distal lower leg
and forearm bones.2 The radiologist evaluated the
radiographs without prior knowledge of the clinical
details. Periostitis was classified as 'minimal' when
the periosteal rise was seen only on close inspection
of the radiograph using bright lamp illumination
(Fig. 2a). Periostitis was classified as 'obvious' when
against a normally
screen (Fig. 2b), and 'florid' when there was sub-
periosteal calcification and fusion with the outer
margin of the bony cortex (Fig. 2c). Patients ex-
cluded from the study were those with unilateral
periostitis, longstanding pedal oedema, and those in
whom severe varicose veins or phlebitis may have
stimulated a periosteal reaction.
for screening purposes,
measuring the nail-nail bed angle (ABC) in patients with
equivocal clinical clubbing (clubbing=ABC>
Representation of the shadowgraph usedfor
Obvious clubbing was present in 190% of patients
with PBC, 21% with CAH, and 170% of patients in
the group of mixed liver diseases. Eleven patients
were judged to have borderline clubbing, and, of
these, five had nail-nail bed angles greater than 1680
(normal mean +SD= 155°+ 8°). Therefore, using the
shadowgraph to differentiate patients with equivocal
clinical clubbing, the overall prevalence of clubbing
was 240% in PBC, 290% in CAH, and 230% in the
group of mixed liver diseases (Table 2).
Symmetrical periostitis affecting the lower leg
bones was present in 35%of patients with PBC, 29%
with CAH, and 40% with other forms of liver
periostitis in the latter group is largely accounted for
by the high prevalence in alcoholic cirrhosis (seven
of 12 patients). Only eight patients (6%) had
periostitis affecting the distal radii and ulnae, and
forearm involvement occurred only in the presence
of leg bone involvement. The tibiae and fibulae were
affected either singly, or together (Table 3). The
periostitis was classified at minimal in 26%, obvious
in 45%, and florid in 29% of affected patients.
The association of clubbing and periostitis
summarised in Table 2. Clubbing and periostitis
occurred together in 2020% of patients with PBC,
4.1 % with CAH, and 6 8%in the group with mixed
liver diseases. Whereas in PBC 83-3% of clubbed
patients had periostitis, only 14.2%of clubbed CAH
patients and 28.5% of clubbed patients in the group
with mixedliverdiseases had
presence of finger clubbing was significantly asso-
ciated with periostitis in PBC (X2 =2425, p <0001),
but not in other forms of chronic liver disease.
In all forms of liver disease, periostitis may be
present without associated clubbing. Forty-two per
cent of PBC patients with periostitis did not have
clubbing, and the corresponding figures for CAH and
miscellaneous liver disease were 85% and 83%
Prospective study ofperiostitis andfinger clubbing in primary biliary cirrhosis
Radiological appearance of (a) minimal, (b) obvious, and (c) floridperiostitis affecting the tibia andfibula.
Twenty-three of the patients studied complained
of arthralgia, and five had rheumatoid arthritis.
Joint pains were not more common in patients with
periostitis than those without periostitis. Bone pain
and tenderness are common symptoms in chronic
liver disease, and may be due to osteoporosis,
o,,er the lower tibiae and fibulae was present in 15
of 45 (33 %) patients with periostitis and only five of
83 (6%) without periostitis (x2= 1450 P <0 001).
this sign was a reliable sign of
There was no association between the duration of
illness and the extent or severity of the periostitis or
clubbing, nor was there a correlation with the degree
of liver dysfunction judged biochemically. In PBC,
periostitis with or without clubbing occurred both
in the precirrhotic and cirrhotic phase of the disease.
between clubbing andperiostitis in each group.
Prevalence ofclubbing andperiostitis in PBC, CAH, and mixed liver diseases (MLD), and relationship
Epstein, Dick, and Sherlock
chronic liver disease*
Bone distribution ofperiostitis in patients with
Tibiae and fibulae
Radii and ulnae
*Results expressed as number of afiected patients. Total number
of patients studied: 128.
In a retrospective study, we suggested that periostitis
be considered in the differential diagnosis of the
skeletal pain in the patients with chronic liver disease
and finger clubbing.2 The observation that periostitis
also occurred in patients with no skeletal symptoms2
prompted this prospective study to determine the
prevalence of periostitis in PBC, and other forms of
chronic liver disease. The results of this study
indicate that periostitis, with or without clubbing,
occurs in about a third of patients with PBC and is
equally common in other forms of chronic liver
disease. The prevalence of finger clubbing was
similar in the groups studied, but only in PBC was
finger clubbing significantly associated with peri-
ostitis. The observation that periostitis commonly
occurs in the absence of finger clubbing indicates
that the two conditions should be sought independ-
ently, and our original conclusion-that for screen-
ing purposes periostitis should be sought in patients
with finger clubbing-is invalid.
In the majority of patients the periostitis affected
only the leg bones. The periostitis was unusually
easy to recognise on a plain anteroposterior radio-
graph of the tibiae and fibulae, but 'minimal'
periostitis was often only diagnosed when the radio-
graph was examined over a bright light.
An unexpected finding was the high prevalence of
periostitis in patients with alcohol-induced cirrhosis.
This study did not include patients with alcohol-
induced fatty liver, fibrosis, or alcoholic hepatitis,
nor did it include alcoholic patients without cirrhosis.
A study of these alcoholic subgroups is presently
under way to determine whether periostitis and
clubbing is associated only with alcohol-induced
cirrhosis, or whether it is an association of chronic
alcohol ingestion, with or without liver injury.
Joint pain was not more common in patients with
periostitis than those without. Marked tenderness
over the lower leg bones was a distinctive sign in a
third of patients with periostitis, and probably
of the pain-sensitive peri-
The results of this study indicate that periostitis is
a common complication of PBC and other forms of
chronic liver disease, and it is often present in the
absence of finger clubbing. The presence of finger
clubbing and skeletal symptoms usually alerts the
clinician to the possibility of associated periostitis.
Only in PBC is the presence of finger clubbing
strongly associated with periostitis, and this observa-
tion probably explains the incorrect impression
from the literature that periostitis is most common in
PBC.' The factors responsible for periostitis and
finger clubbing in patients with chronic liver disease
are unknown. In particular, there is no evidence that
hormonal or cardiopulmonary factors are involved.2
Periostitis should be considered in the differential
diagnosis of bone pain and tenderness in patients
with chronic liver disease, and its presence should be
sought whether or not the patient has finger clubbing.
(Clinical and General) Ltd, and Mr A Chester
1Whelton MJ. Arthropathy and liver disease. Br J Hosp
Med 1970; 3: 343-7.
2Epstein 0, Ajdukiewicz AB, Dick R, Sherlock S. Hyper-
trophic hepatic osteoarthropathy. Clinical, roentgen-
ologic, biochemical, hormonal and cardiorespiratory
studies and review of the literature. Am JMed 1979; 67:
3Pyke DA. Clinical assessment of clubbing. Lancet 1954;
4Bentley D, Cline J. Estimation ofclubbing by analysis of
the shadowgraph. Br MedJ 1970; 3: 43.