close

Вход

Забыли?

вход по аккаунту

?

Hypertrophic osteoarthropathy in cyanotic congenital heart disease. its prevalence and relationship to bypass of the lung

код для вставкиСкачать
1186
HYPERTROPHIC OSTEOARTHROPATHY IN
CYANOTIC CONGENITAL HEART DISEASE
Its Prevalence and Relationship to Bypass of the Lung
MANUEL MARTINEZ-LAVIN, MARIA BOBADILLA, JOSE CASANOVA, FAUSE ATTIE, and
MARC0 MARTINEZ
The frequency of hypertrophic osteoarthropathy
in cyanotic congenital heart disease has previously been
considered to be very low. Only a few isolated reports
have described such an association. We studied 32
consecutive patients older than 6 years with various
types of cyanotic congenital heart disease and examined
each case for hypertrophic osteoarthropathy. We also
assessed the role of the altered cardiopulmonary hemodynamics in the development of hypertrophic osteoarthropathy by means of cardiac catheterization. Our results showed that 31% of the patients had hypertrophic
osteoarthropathy. When the hemodynamic parameters
of the group of patients with hypertrophic osteoarthropathy were compared with those of the remaining patients, we found significant differences in the systemic
blood flow (PI0.05), right-to-left shunt (PI0.05), and
arterial oxygen unsaturation (P I0.005). Thus, we
found a much higher prevalence of hypertrophic osteoarthropathy in patients with cyanotic congenital heart
disease than has previously been recognized. The development of hypertrophic osteoarthropathy is related to
the degree of bypass of the lung. This is consistent with
From the Instituto Nacional de Cardiologia Ignacio Chavez, Mtxico City, MCxico.
Manuel Martinez-Lavin, MD, FACP: Clinical Investigator,
Rheumatology Service, Instituto Nacional de Cardiologia Ignacio
Chavez; Maria Bobadilla MD: Rheumatology Fellow, Instituto
Nacional de Cardiologia Ignacio Chavez; Jose Casanova: Biostatistician, Instituto Nacional de Cardiologia Ignacio Chavez; Fause
AttiC, MD, FACP: Head of the Pediatric Cardiology Service,
Instituto Nacional de Cardiologia Ignacio Chavez; Marco Martinez,
MD, FACP: Hemodynamic Department, Instituto Nacional de
Cardiologia Ignacio Chavez.
Address reprint requests to Manuel Martinez-Lavin, MD,
FACP, Rheumatology Service, Instituto Nacional de Cardiologia
Ignacio Chavez, Juan Badiano #I, MCxico 22 DF, MCxico.
Submitted for publication December 7, 1981; accepted in
revised form April 14, 1982.
Arthritis and Rheumatism, Vol. 25, No. 10 (October 1982)
the concept that hypertrophic osteoarthropathy results
from mediators in the systemic venous circulation that
escape inactivation in the pulmonary capillary bed.
Although digital clubbing is common in patients
with cyanotic congenital heart disease (CCHD), hypertrophic osteoarthropathy (HOA) has rarely been
reported in this condition. In two standard textbooks
of internal medicine (1-3), the association of HOA and
CCHD is given little attention. Harrison (1) mentions
only in passing that HOA may occur in CCHD. Cecil
(2) lists it with lung cancer, mesothelioma, and bronchiectasis, but omits mention of it with CCHD. The
English language literature does contain a few isolated
reports of HOA associated with CCHD (4-8). Trever
(6) quoted Helen Taussig that only 3 cases of HOA
were seen at the Harriet Lane Home in 3,000 patients
with CCHD. It seems to us, however, that the true
frequency of HOA in CCHD has never been properly
assessed, since many cases may have been missed or
ignored by physicians far more interested in the heart
than the joints.
In the present study, we investigated the prevalence of HOA in CCHD patients over 6 years old in
our institution. We also assessed the role of the altered
cardiopulmonary hemodynamics in the development
of HOA by means of cardiac catheterization.
PATIENTS AND METHODS
We studied 32 consecutive CCHD patients older than
6 years w h o were admitted t o our institution for evaluation
of their heart conditions. T h e age limit was set arbitrarily; all
previously reported cases were older than 6 years (4) and
also, with this age limit, the clinical and x-ray assessments
are more accurate. E a c h patient had a complete history and
OSTEOARTHROPATHY IN CONGENITAL HEART DISEASE
1187
B
A
Figure 1. Roentgenograms taken of the left forearm of Patient 9. A , Before surgery, radiolucent line (arrows) is present beneath the periostium
of the ulna; B, 4 months after surgery, periostitis is absent.
physical examination with emphasis on musculoskeletal
abnormalities. Laboratory examination included complete
blood count, blood chemistry, uric acid, and urinalysis. Xray examination consisted of a full skeletal survey. Cardiac
catheterization was performed for all patients; arterial oxygen saturation was determined in 28; 25 were evaluated for
systemic blood flow, effective pulmonary blood flow, and
right-to-left shunt. Estimations of flows were not done in 7
patients because of technical difficulties during the procedure (inability to enter the pulmonary artery, patient breathing oxygen). Cardiac output was determined according to
Fick’s formula (9) utilizing the IL Co-oxymeter (Instrumentation Laboratory, Lexington, MA). Calculations were done
as follows:
systemic blood flow (litershinutes) =
oxygen consumption ( m h i n u t e s )
(0, content systemic artery O2 content mixed venous return) x 10
pulmonary blood flow (litershinutes)
effective pulmonary blood flow (litershinutes) =
oxveen consumotion (ml/minutes)
( 0 2 content pulmonary vein O2 content mixed venous return) X 10
right-to-left shunt = systemic blood flow - effective pulmonary
blood flow
left-to-right shunt = pulmonary blood flow - effective pulmonary
blood flow
The oxygen consumption was calculated according
to the table by LaFarge and Miettinen (10). The error
between observed and predicted values using this method
has a standard deviation of less than 28 (ml/minutes) square
meters which is considered to be an adequate way to
measure flows (9).
Our criteria for diagnosing HOA required the combined presence of digital clubbing, arthritis, and radiologic
evidence of periostitis manifested as a radiolucent line
beneath the periostium of the long bones (Figure IA) or as
roughened irregular “lacey” periostium (Figure 2A).
=
oxvgen
- - consumption ( d m i n u t e s )
(0, content pulmonary vein 0, content pulmonary artery) X 10
RESULTS
Ten of the 32 patients (31%) had hypertrophic
osteoarthropathy. The salient clinical features of the
MARTiNEZ-LAVIN ET AL
1188
A
B
C
D
Figure 2. A, Anteroposterior view of Patient 6’s forearms showing irregular lacey periostium (arrows). B, Anteroposterior.view of Patient 7’s
left ankle showing “whiskering” of the tibia (arrow). C, Anteroposterior view of Patient 8’s right ankle showing periostitis of the fibula (arrow).
D, Anteroposterior view of Patient 10’s right ankle showing periostitis of the tibia (arrows).
patients with HOA are analyzed in Table 1. A representative radiograph demonstrating periostitis in each
patient is depicted in Figures 2-4. The arthritis was
symmetric and persistent. It involved mainly the large
joints of the lower extremities and was accompanied
by periarticular soft tissue swelling. This soft tissue
swelling was more conspicuous when the ankles were
involved. In these instances, the legs took on a cylindrical shape resembling “elephant feet.” The swelling
was non-pitting and not ascribable to right heart failure. Right atrial pressures of the patients with HOA
were similar to the other patients (7.8 ? 4.5 versus 6.3
2.2 [mean +- SD]).
When the 10 patients with HOA were grouped
*
OSTEOARTHROPATHY IN CONGENITAL HEART DISEASE
Table 1. Clinical features of the 10 patients with hypertrophic
osteoarthropathy
Patient
Clubbing
Arthritis
Periostitis
1
2
3
+
+
++
+
+
+
+
+
+
Ankles
Ankles
Knees, ankles
Knees
Knees, ankles
Knees, ankles
Ankles
Shoulders
Knees, ankles
Knees
Tibias, feet
Fibulas
Generalized
Tibias, fibulas
Fibulas, feet
Generalized
Tibias, fibulas
Tibias, fibulas
Generalized
Tibias, fibulas
4
5
6
7
8
9
10
together and compared with the 22 remaining patients
by means of the Student’s t-test (Table 2), there was
no significant difference in sex, age, levels of hemoglobin, or hematocrit; there was, however, a significant
difference in systemic blood flow (P I0.05), right-toleft shunt (P5 0.05), and arterial oxygen unsaturation
(P5 0.005). Hyperuricemia (uric acid above 8 mg/dl),
a well known complication of the polycythemia that
occurs in CCHD (1l), was found in 11 patients (5 with
HOA, 6 without HOA); 4 of the 6 patients without
HOA also had gouty arthritis. Two patients with HOA
also had gout (these 2 patients will be described in
detail in another article).
Fifteen of the 32 patients studied underwent
corrective or palliative heart surgery. Surgery was not
performed in the remaining 17 because of the presence
of pulmonary hypertension, precarious general condition, or patient refusal. Of the 10 patients with HOA,
only 1 was amenable to corrective procedure. Two
others had had palliative surgery in the past. The
patient in whom a definite procedure was performed is
described below to stress that correction of the rightto-left shunt in CCHD may improve HOA,just as does
correction of other lesions known to cause HOA (12).
Case report. A 14-year-old boy was referred for
evaluation of his heart condition. He had had cyanosis
since birth, dyspnea on exertion from the time he
started to walk, and frequent episodes of pneumonia
during childhood. In the last year, he noticed aching of
both knees and ankles and along the tibia1 shafts,
accompanied by diffuse swelling of both legs. In the
review of systems, there were no other data suggestive
of systemic rheumatic disease.
At physical examination, deep universal cyanosis, marked clubbing of the 20 digits, and pectum
carinatum were found. On examination of the heart,
the point of maximal impulse was in the fifth left
1189
intercostal space 2 cm outside the midclavicular line.
There was a parasternal thrill and a grade III/IV
systolic murmur best heard at the second right intercostal space. There was no palpable abdominal organomegaly. The legs, with diffuse swelling, resembled
“elephant feet.” Joint examination showed swelling of
both knees and ankles.
Synovial fluid aspirated from the right knee was
viscous -with less than 1,000 leukocytes per cubic
centimeter. No crystals were seen with the polarized
microscope. Bone radiographs showed diffuse periostitis most apparent in the ulnas, tibias, fibulas, and
metatarsal bones (Figure 1A). On laboratory examination the hemoglobin was 22, hematocrit 73, uric acid
10.9, urinalysis 0.18 gm of protein per liter, and
rheumatoid factor was negative. Cardiac catheterization showed transposition of the great vessels, pulmonary stenosis, and ventricular septal defect. The systemic blood flow was 7.5 1 litedminute, effective
pulmonary blood flow 1.7 1 litedminute, right-to-left
shunt 5.80 litedminute, and arterial oxygen saturation
72%.
The patient underwent heart surgery. The ventricular septal defect was obliterated, and a dacron
tube was inserted communicating the right ventricle to
the pulmonary artery. Five days after surgery, the soft
Figure 3. Anteroposterior view of Patient 1’s right foot showing
periostitis of the fifth metatarsal (arrow).
MARTINEZ-LAViN ET AL
1190
A
B
C
D
Figure 4. A, Anteroposterior view of Patient 2’s right ankle showing periostitis of the fibula (arrow). B, Lateral view of Patient 3’s left knee
showing periostitis of the femur (arrows). C , Anteroposterior view of Patient 4’s left leg showing periostitis of the fibula (arrows). D,
Anteroposterior view of Patient 5’s left leg showing periostitis of the fibula (arrows).
tissue swelling and the arthritis had disappeared and
his general condition improved. One month after surgery, repeated cardiac catheterization showed an incomplete closure of the ventricular septa1 defect.
Systemic blood flow was 5.01 liter/minute, effective
pulmonary blood flow 3.61 litedminute, right-to-left
shunt 1.40 litedminute, and arterial oxygen saturation
83%. Examination 4 months after surgery demonstrated decreased clubbing of the digits and no arthritis.
Radiographs of the bones demonstrated disappearance
of the periostitis (Figure 1B).
To our knowledge, this is the first reported case
OSTEOARTHROPATHY IN CONGENITAL HEART DISEASE
1191
Table 2. Clinical and hemodynamic features of the 32 patients*
Patient
Sexlage
Heart disease
Patients with hypertrophic osteoarthrooathv
,
,
Patent ductus, reverse
1
F111
flow
Univentricular heart
2
Fl19
Situs ambiguous
3
Fl2 1
Fallot
4
F111
TGA, pulmonary
5
MI10
stenosis
TGA, pulmonary
6
MI45
stenosis
Fallot
1
MI28
Atrial septal defect,
8
Fl27
pulmonary hypertension
TGA, pulmonary
9
MI14
stenosis
Double outlet
10
MI16
Mean 2 SD
20.8 2 10.4
Patients without hypertrophic osteoarthrooathv
. <
TGA, pulmonary
11
MI10
stenosis
TGA
12
MI21
Fallot
13
MI16
Patent ductus, reverse
14
MI29
flow
Fallot
15
MI15
Fallot
16
MI1
Anomalous venous
17
MI27
connection
AV canal
18
MI15
Ebstein, atrial septal
19
Fl30
defect
Pulmonary AV fistulae
20
MI8
Pulmonary AV fistulae
21
MI15
Fallot
22
F113
TGA, pulmonary
23
FI11
stenosis
Univentricular heart
24
MI9
TGA, pulmonary
25
F19
stenosis
Fallot
26
MI24
Fallot
21
F/8
Atrial septal defect,
28
F111
pulmonary hypertension
Fallot
29
FI11
Fallot
30
Fl9
Patent ductus, reverse
31
F138
flow
Fallot
32
MI16
Mean ? SD
16.3 2 8.82
PS
NS
Hblhct
Syatemic
blood flowt
Effective
pulmonary
blood flowt
Right-to-left
shuntt
16/60
6.0
I .2
4.8
61
17/58
18162
22164
16/58
5.7
8.0
5.6
5.0
1.8
1.8
1.2
I .4
3.9
6.2
4.4
3.6
63
27
64
64
19/67
16.8
3.5
13.3
65
25183
17/58
2.9
13.8
2.3
5.2
0.6
8.6
79
62
22173
7.5
I .7
5.8
72
20172
19.2 2 3.011
65.5 ? 8.30
ND
7.92 2 4.49
ND
2.23 ? 1.32
ND
5.69 2 3.56
58
61.50 2 13.53
Arterial O2
saturation (96)
19162
4
2.9
1.1
88
19163
17/63
21171
2.5
ND
4.8
2.0
ND
2.4
0.5
ND
2.4
82
74
76
19/60
20167
21171
3.3
ND
5.8
2.4
ND
3.0
0.9
ND
2.8
81
ND
68
18161
22172
9.3
4.8
3.4
2.3
5.9
2.5
81
83
13/46
19151
I8154
16/52
2.7
ND
ND
2.8
1.6
ND
ND
2.1
1.1
ND
ND
0.7
72
ND
72
20167
19/57
5.3
4.9
2.1
2.5
3.2
2.4
75
80
24179
19154
16154
2.8
2.8
4.0
2.2
2.7
2.3
0.6
0.1
1.7
87
80
78
18/54
22176
I9170
3.9
ND
ND
2.5
ND
ND
I .4
ND
ND
83
ND
ND
14/48
18.76 2 2.561
61.45 t 9.30
4.8
4.28 t 1.69
2.3
2.42 t 0.43
NSINS
0.05
NS
* Hb/hct = hemoglobinlhematocrit; F = female; M = male; TGA
determined; SD = standard deviation; NS = not significant.
t Values given in literslminute.
=
transposition of the great arteries; AV
no
68
2.5
1.86
2
1.43
0.05
=
78.82
?
5.40
0.001
atrioventricular; N D
=
not
MARTINEZ-LAViN ET AL
1192
in which correction of the congenital heart problem led
to the disappearance of the periostitis and arthritis.
The fact further supports the evidence that in CCHD
the right-to-left shunt is a determining factor in the
development of HOA.
DISCUSSION
Our findings of a 31% frequency of hypertrophic osteoarthropathy in cyanotic congenital heart
disease in this series in our institution is astonishingly
different from the lower prevalence described in past
series (6). This discrepancy may be due to several
factors. The age limit that we set eliminated milder
cases of CCHD amenable to surgery in patients who
may not be old enough or sick enough to develop
HOA. Also in this type of patient, the severity of the
cardiopulmonary abnormalities can overshadow the
arthritic symptoms, and the soft tissue swelling may be
falsely ascribed to heart failure. Three of our patients
had such obvious symptoms of hypertrophic osteoarthropathy that it would be surprising if the correct diagnosis could have been missed or ignored in
other clinics. The other 7 had more subtle symptoms
that might have been misdiagnosed except for our
particular interest in detecting the syndrome.
If HOA is truly more frequent in CCHD in our
clinic than in others, then one could consider several
other possible factors in the difference. 1) Our Mexican population is largely a mixture of Spanish and
Indian, Correspondingly, this group may have different genetically controlled responsiveness to environmental and other factors. 2) Our patients may have had
more intense and protracted difficulty with CCHD
before coming to the clinic for care than is usual in
other clinics. As can be seen in Table 2, the systemic
arterial oxygen unsaturation of the patients with HOA
was severe. Of the patients with CCHD and HOA
described in the literature, the oxymetry studies are
given for only 2; these 2 patients were also found to be
severely hypoxemic. Williams et a1 (7) reported a case
of patent ductus with pulmonary hypertension in
which the 0 2 saturation of the femoral artery was 63%.
In the patient described by Dailey et a1 (8), the
saturation of the arterial O2 can be calculated at 59%.
Since the original description by Bamberger
(13) and Marie (14), several theories have been put
forward to explain the pathogenesis of HOA, none of
them conclusive (15). Among these theories is one that
proposes that finger clubbing is developed by the
presence in the systemic circulation of a substance
normally inactivated or removed in the lung, such as
reduced ferritin (16) or prostaglandin E (17). One could
add gut-derived immune complexes as a further theoretical consideration.
There are also animal experiments suggesting
that bypass of the lung is responsible for the development of HOA. Mendlowitz and Leslie (18) reported in
1942 that after many unsuccessful trials, they were
able to surgically produce right-to-left shunt in dogs by
anastomosing the pulmonary artery to the left atrium.
The 4 dogs with the highest systemic output developed
HOA. The authors concluded that HOA was due to
“forced feeding” of the bones secondary to the increased output. Gerbode et a1 (19) did similar studies
on 3 dogs, anastomosing the inferior vena cava to the
left atrium. Two dogs developed HOA, both of which
had lower arterial oxygen saturation (66% and 54%)
compared with the one that did not develop HOA
(75%).
The results of our study indicate that the development of HOA in patients with CCHD is related to
arterial oxygen unsaturation, increased systemic output, and severe right-to-left shunt. This suggests to us
that the degree of lung bypass is the most significant
factor in the pathogenesis of hypertrophic osteoarthropathy and supports the concept that HOA in
cyanotic congenital heart disease results from mediators in visceral venous circulation that escape inactivation or removal in the pulmonary capillary bed.
ACKNOWLEDGMENT
The helpful advice of Dr. John Vaughan is gratefully
acknowledged.
REFERENCES
Mannik M, Gilliand B: Miscellaneous arthritides and
extra-articular rheumatism, Harrison’s Principles of Internal Medicine. Ninth edition. Edited by K Isselbacher,
A Adams, E Braunwald, R Petersdorf, J Wilson. Philadelphia, McGraw Hill, 1980, pp 1900-1904
Christian C: Miscellaneous forms of arthritis, Cecil
Textbook of Medicine. Fifteenth edition. Edited by P
Beeson, W McDermott, J Wyngaarden. Philadelphia,
WB Saunders Co, 1979, pp 200-208
Avioli L: Hypertrophic osteoarthropathy, Cecil Textbook of Medicine. Fifteenth edition. Edited by P Beeson, W McDermott, J Wyngaarden. Philadelphia, WB
Saunders Co, 1979, p 2263
OSTEOARTHROPATHY IN CONGENITAL HEART DISEASE
4. Olu G, Olu M: Hypertrophic osteoarthropathy associated with Fallot’s tetralogy: a case report. Postgrad Med J
51:648-653, 1975
5. McLaughin G, McCarty D, Downing DF: Hypertrophic
osteoarthropathy associated with cyanotic congenital
heart disease. Ann Intern Med 67579-587, 1967
6. Trever RW: Hypertrophic pulmonary osteoarthropathy
in association with congenital cyanotic heart disease.
Ann Intern Med 48:660-668, 1958
7. Williams B, Ling JT, Leight L , McGaff CJ: Patent
ductus arteriosus and osteoarthropathy. Arch Intern
Med 111:346-350, 1963
8. Dailey FH, Genovese PD, Behnke RH: Patent ductus
arteriosus with reversal of flow in adults. Ann Intern
Med 56:865-882, 1962
9. Yang S,Bentivoglio L, Maranhao V, Goldberg H: From
cardiac catheterization to hemodynamic parameters.
Philadelphia, FA Davis, 1978, pp 209-301
10. LaFarge CG, Miettinen 0s: The estimation of oxygen
consumption. Cardiovasc Res 4:23-30, 1970
11. Yu T,Weissmann B, Sharney L, Kupfer S, Gutman A:
On the biosynthesis of uric acid from glycine-N in
primary and secondary polycythemia. Am J Med
21:901-917, 1956
1193
12. Holling E, Brodey R: Pulmonary hypertrophic osteoarthropathy. JAMA 178:977-982, 1961
13. Bamberger E: Uber knochenveranderugenn bei chronischen lungen und herzkrankheiten. Z Klin Med 18:193217, 1891
14. Mane P: De l’osteoartrophic hypertrophiante pneumonique. Rev Med 1O:l-36, 1890
15. Howell D: Hypertrophic osteoarthropathy, Arthritis and
Allied Conditions. Ninth edition. Edited by DJ
McCarty. Philadelphia, Lea & Febiger, 1979, pp 977-982
16. Hall GH: The cause of digital clubbing. Lancet 1:750753, 1959
17. Lemen RJ, Gates AJ, Mathe A, Waring W, Hyman A,
Kadowitz D: Relationship among digital clubbing, disease severity, and serum prostaglandins F2 and E in
cystic fibrosis patients. Am Rev Resp Dis 117:639-645,
1978
18. Mendlowitz M, Leslie A: The experimental simulation
in the dog of cyanosis and hypertrophic osteoarthropathy which are associated with congenital heart disease.
Am Heart J 24:141-152, 1942
19. Gerbode F,Birnstingl M, Braimbridge M: Experimental
hypertrophic osteoarthropathy. Surgery 60: 1030-1035,
1966
Документ
Категория
Без категории
Просмотров
2
Размер файла
650 Кб
Теги
cyanotic, osteoarthropathy, lung, bypass, heart, disease, hypertrophic, congenital, relationships, prevalence
1/--страниц
Пожаловаться на содержимое документа