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Aortic insufficiency in association with juvenile ankylosing spondylitis
78
Brief clinical and laboratory observations
The Journal of Pediatrics July 1979
Table L S u m m a r y o f l a b o r a t o r y studies, first admission
Plasma renin activity (ng/ml/hr)
Conditions (see tex 0 Basal Sodium restriction Oral sodium load Dexamethasone administration
0.02 0.23 0.04 0.05
Urinary aldosterone (ng/ml) < < < <
2.5 2.5 2.5 2.5
Plasma deoxycorticosterone (pg/ml)
Plasma I 17-hydroxyprogesterone (ng / ml)
Plasma cortisol (t~g/ dl)
85 (normal = 50-200 pg/ml) 189 76 < 10
0.23 (normal < 1 ng/ml) 0.87 0.24 0.05
17.5 9.5 15.5 Undetectablc
Table II. R e d b l o o d cell ~2Na influx Control (2) Patient (2)
3.7 _+ 0.2 mEq/1 RBC/hr 6.5 _+ 0.5 mEq/1 RBC/hr
~Na 9 influx in erythrocytes from the patient. Number of experiments in parentheses. Values were determined in duplicate and expressed as mean _+ 1 SEM. vitro m e a s u r e m e n t o f 22Na influx into red blood cells will establish the diagnosis o f Liddle s y n d r o m e p r i o r to therapy in patients who h a v e h y p e r t e n s i o n a n d hypokalemia w i t h o u t d e m o n s t r a b l e r e n a l or adrenal pathology. T h e d e m o n s t r a t i o n o f increased t r a n s p o r t o f s o d i u m into erythrocytes a n d the a b s e n c e of mineralocorticoid excess
s u p p o r t the view that Liddle s y n d r o m e is due to a generalized m e m b r a n e abnormality. REFERENCES 1.
Liddle GW, Bledsoe T, and Coppage WS: A familial renal disorder simulating primary aldosteronism but with negligible aldosterone secretion, in Baulieu EE, and Robel P, editors: Aldosterone, Philadelphia, 1964, FA Davis Company, pp 353-368. 2. Gardner J D , Lapey A, Simopoulos AP, and Bravo EL: Abnormal membrane sodium transport in Liddle's syndrome, J Clin Invest 50:2253, 1971. 3. Romualdez A, Sha'afi RI, Lange Y, and Solomon AK: Cation transport in dog red cells, J Gen Physiol 60:46, 1972.
Aortic insufficiency in association with juvenile ankylosing spondylitis Graham D. Reid, M.B., Ch.B.,* Michael W. H. Patterson, M.B., M.R.C.P., C.R.C.P.(C), A. Caroline Patterson, M.B., M.R.C.P., F.R.C.P.,(C), and Peter L. Cooperberg, M.D., Vancouver, B.C., Canada
A O R T I C I N S U F F I C I E N C Y is a recognized cardiac c o m p l i c a t i o n o f ankylosing spondylitis but has not b e e n previously d o c u m e n t e d in childhood. T h e echocardiographic features m a y be distinctive a n d prove helpful in e v a l u a t i n g the etiology o f aortic insufficiency in a given patient in w h o m a r e l a t i o n s h i p with ankylosing spondylitis is u n d e r consideration. CASE REPORT This male, white child was born in 1965. His health was unremarkable until the age of 6 years when, because of aching legs at night, a diagnosis of"growing pains" was made. There was
From the Departments of Medicine, Pediatrics, and Radiology, University of British Columbia. Dr. Reidfunded by The Arthritis Society, B.C. Division. *Reprint address, The Arthritis Society, 895 14L lOth Ave., Vancouver, B.C. V5Z 1L7.
no history of rheumatic fever. At age 9 he was running poorly and his back was noted to have restricted mobility. Subsequently he developed pains in both knees, with an effusion and flexion deformity of the left knee. In May, 1975, the left knee was manipulated with the child under anesthesia. The anesthetist heard a cardiac murmur and the child was admitted for investigation. His father had psoriasis, but there was no other relevant family history. On examination his height was 138 cm and weight 30.5 kg. He was slightly pale and looked unwell, but had no evidence of iritis or rash. Peripheral pulse volume was increased and his blood pressure was 110/50, He had a visible left ventricular impulse outside the midclavicular line, with an associated heave, but no thrill. The first and second heart sounds were normal, with a Grade 2/6 ejection systolic murmur in the aortic area and neck, and a Grade 4/6 decrescendo diastolic murmur in the third and fourth left interspaces. There was no evidence of cardiac failure.
0022-3476/79/070078 +03500.30/0 9 1979 The C. V. Mosby Co.
Volume 95 Number 1
Brief clinical and laboratory observations
79
Fig. 1. M-mode '!sweep" from aortic root toward LV apex showing thickened echoes (arrowhead) superimposed over anterior mitral leaflet echo near the mitral ring.
Musculoskeletal examination showed a normal hip range but a marked reduction in mobility o f the lower spine, as evidenced by loss o f lumbar lordosis, flattening of the lumbar spine noted on attempted forward flexion, and reduction of forward flexion such that his finger tips reached only to the level of the tibial tubercles. There was wasting of the left quadriceps and calf muscles with a flexion deformity and effusion in his left knee, and a painful effusion o f his left ankle. There were also thickening and tenderness of the interphalangeal joint of his right thumb and metacarpophalangeal joint of his left index finger. Investigations. The hemoglobin was 11.0 gm/dl and the erythrocyte sedimentation rate 55 mm/hour. Results of tests for ANF, VDRL and RA Latex were all negative. The ASO titer was 50 Todd units/ml, and urinalysis was normal. HLA B-27 antigen was detected by tissue typing. Radiologically the sacroiliac joints were definitely abnormal: o n the iliac side of both joints there was sclerosis, which increased between 1974 and 1978, and there were erosions o f the right joint. Radiographs Of the spine were normal. Chest radiographs showed a moderately enlarged cardiac outline with a prominent left ventricular contour. The electrocardiogram showed sinus rhythm with normal conduction. A deep S in V o and tall R in V6 ( = 70 mm) suggested left
ventricular hypertrophy, but there was no evidence of strain. Echocardiography, using a 5 megahertz 6 mm diameter transducer, showed a normal aortic valve with a discrete central diastolic closure line. The aortic root was mildly dilated at 2.8 cm ( N = i.87 + 0.19) as was the left ventricle at 5.4 cm (N = 3,62 + 0.35) but contractility appeared normal. There was a diastolic flutter of both mitral valve leaflets and a thick echo complex related to the anterior mitral leaflet near the mitral ring (Fig. 1). Real time sector scans were obtained with a Picker Cardiac image r using a 5 megahertz 6 mm diameter short internal focus transducer. These showed thickening o f the anterior mitrat leaflet near the root of the aorta, identified as a "bump" !n Fig. 2. A linear echo anterior to the mitral valve was thought to be part of the chordal apparatus. Cardiac catheterization. Right and'retrograde left heart catheterization under sedation with meperidine revealed normal pressures and oxygen saturation values. There were no shunts on hydrogen ion potentiometric studies and there was a probe patent foramen ovale. Left ventricular angiograms in the LAO and RAO projections showed a dilated left ventricle, and a tricuspid aortic valve of which the right coronary cusp appeared more rigid. The mitral valve was competent and there appeared to be a
80
Brief clinical and laboratory observations
Fig. 2. Real time cross sectional echocardiogram in the sagittal plane lllust(ates thickening on anterior mitral leaflet at the base of the aorta, identified as "bump.!' AOR = Aortic root; AML = anterior mitral leaflet; IVS = interventricular septum; LA = left atriumi LV = left ventricle~ PML = post mitral leaflet. bump in the region of the anterior leaflet. The aortograms demonstrated normal coronary arteries and a moderately dilated root with aortic insufficiency (§ to +3) without cusp prolapse. DISCUSSION This patient has the cardinal features of ankylosing spondylitis, including pain, stiffness, and immobility of the back ~ with radiologic evidence of sacroiliitis. Ankylosing spondylitis has its m a x i m u m incidence in males between the ages of 20 and 40 years, 1 but a small series have been reported in children. 2-4 Ladd et al 2 noted that ankylosing spondylitis occurred in 7% of children seen for chronic arthritis, making this diagnosis unusual but not rare in children. In addition to the spine, our patient also had peripheraljo!nt !nvolvement, which is consistent with anky• losing spondylitis of early onset. Wilkinson and Bywaters 1 found the incidence of peripheral joint involvement in spondylitis With onset before age 20 was 40%, compared with 22% in those with onset after the age of 20. Like ankylosing sp0ndylitis, acquired aortic regurgitation is predominantly a disease of adult males. In childhood it is usually a sequel of acute rheumatic fever, and less commonly the result of bacterial endocarditis or associated with Marfan syndrome. In our patient the typical findings of aortic regurgitation with the joint manifestations of spondylitis made a c o m m o n etiology likely. Although rheumatic fever was suspected initially, the clinical and laboratory evidence did not substantiate this. The association between aortic insuff• and anky-
The Journal of Pediatrics July 1979 losing spondylitis was originally described by Bauer et al. 6 The prevalence of aortic insufficiency increases with the duration of the spondylitis, occurring in up to 10% of patients after 30 years, 6. 8. 9 but p a t i e n t s have been described in whom the lesion preceded the onset of spondylitis?. 7 Bulkley and Roberts 7 discussed the pathology of aortic regurgitation in ankylosing spondylitis. They described extension of the fibrous thickening of the wall of the aorta and its valve cusps onto the base of the anterior mitral leaflet, with a resultant ridge or " b u m p . " The extra echoes anterior to the mitral valve leaflet in Fig. 1 most likely represent this thickening, and the left ventricular anglogram and sector scan (Fig. 2) further support this interpretafion. The findings in our patient closely resemble those described in adults with ankylosing spondylitis and aortic insufficiency. The m a n a g e m e n t of this boy's cardiac disease is presently confined to prophylaxis against infective endocarditis. No restrictions of his activity are required because it is already quite limited by joint disease, which is managed with anti-inflammatory agents and physical therapy. The cardiac prognosis m children remains uncertain but it is reassuring to find that lack of progression ~ and a successful surgical repair have been reported in adults. TM Others are less optimistic, giving a 50% survival time o f seven years after the appearance of aortic insufficiency? The authors thank Dr. R. H. Hill for allowing them to report this case. REFERENCES
1
2. 3. 4. 5.
6.
7. 8. 9.
10.
Wilkinson M. and Bywaters EGL: Clinical features and course o f ankylosing spondylitis. Ann Rheum Dis 17:209. 1958. Ladd JR. Cassidy JT. and Martel W: Juvenile ankylosing spondylitis. Arthritis Rheum 14:579. 1971. Jacobs P: Ankylosing spondylitis in children and adolescents. Arch Dis Child 38:492. 1963. Schaller J, Bitnum S. and Wedgewood RJ: Ankylosing spondylitis with childhood onset. J PEDIATR74:505. 1969. Riley MJ, Ansell BM, and Bywaters EGL: Radiological manifestations of ankylosing spondylitis according to age at onset. Ann Rheum Dis 30:138, 1971. Bauer W. Clark WS. and Kulka JP: Aortitis and aortic endocarditis an unrecognized manifestation of rheumatoid arthritis. Ann Rheum Dis 10:470. 1951. Bulkley BH, and Roberts WC~ Ankylosing spondylitis in aortic regurgitation, Circulation 48:1014, 1973. Graham DC, and Smythe HA: The carditis and aortitis of ankylosing spondylitis. Bull Rheum Dis 9:171. 1958. Kinsella TD. Johnson LG. and Sutherland RI: Cardiovascular manifestations of ankylosing spondylitis. Can Med Assoc J 111:1309. 1974. Spitzer S, Peguero F. and Manson D: Rheumatoid spondylitis, aortic insufficiency and coronary artery disease. Chest 68:828, 1975.
Brief clinical and laboratory observations
The Journal of Pediatrics July 1979
Table L S u m m a r y o f l a b o r a t o r y studies, first admission
Plasma renin activity (ng/ml/hr)
Conditions (see tex 0 Basal Sodium restriction Oral sodium load Dexamethasone administration
0.02 0.23 0.04 0.05
Urinary aldosterone (ng/ml) < < < <
2.5 2.5 2.5 2.5
Plasma deoxycorticosterone (pg/ml)
Plasma I 17-hydroxyprogesterone (ng / ml)
Plasma cortisol (t~g/ dl)
85 (normal = 50-200 pg/ml) 189 76 < 10
0.23 (normal < 1 ng/ml) 0.87 0.24 0.05
17.5 9.5 15.5 Undetectablc
Table II. R e d b l o o d cell ~2Na influx Control (2) Patient (2)
3.7 _+ 0.2 mEq/1 RBC/hr 6.5 _+ 0.5 mEq/1 RBC/hr
~Na 9 influx in erythrocytes from the patient. Number of experiments in parentheses. Values were determined in duplicate and expressed as mean _+ 1 SEM. vitro m e a s u r e m e n t o f 22Na influx into red blood cells will establish the diagnosis o f Liddle s y n d r o m e p r i o r to therapy in patients who h a v e h y p e r t e n s i o n a n d hypokalemia w i t h o u t d e m o n s t r a b l e r e n a l or adrenal pathology. T h e d e m o n s t r a t i o n o f increased t r a n s p o r t o f s o d i u m into erythrocytes a n d the a b s e n c e of mineralocorticoid excess
s u p p o r t the view that Liddle s y n d r o m e is due to a generalized m e m b r a n e abnormality. REFERENCES 1.
Liddle GW, Bledsoe T, and Coppage WS: A familial renal disorder simulating primary aldosteronism but with negligible aldosterone secretion, in Baulieu EE, and Robel P, editors: Aldosterone, Philadelphia, 1964, FA Davis Company, pp 353-368. 2. Gardner J D , Lapey A, Simopoulos AP, and Bravo EL: Abnormal membrane sodium transport in Liddle's syndrome, J Clin Invest 50:2253, 1971. 3. Romualdez A, Sha'afi RI, Lange Y, and Solomon AK: Cation transport in dog red cells, J Gen Physiol 60:46, 1972.
Aortic insufficiency in association with juvenile ankylosing spondylitis Graham D. Reid, M.B., Ch.B.,* Michael W. H. Patterson, M.B., M.R.C.P., C.R.C.P.(C), A. Caroline Patterson, M.B., M.R.C.P., F.R.C.P.,(C), and Peter L. Cooperberg, M.D., Vancouver, B.C., Canada
A O R T I C I N S U F F I C I E N C Y is a recognized cardiac c o m p l i c a t i o n o f ankylosing spondylitis but has not b e e n previously d o c u m e n t e d in childhood. T h e echocardiographic features m a y be distinctive a n d prove helpful in e v a l u a t i n g the etiology o f aortic insufficiency in a given patient in w h o m a r e l a t i o n s h i p with ankylosing spondylitis is u n d e r consideration. CASE REPORT This male, white child was born in 1965. His health was unremarkable until the age of 6 years when, because of aching legs at night, a diagnosis of"growing pains" was made. There was
From the Departments of Medicine, Pediatrics, and Radiology, University of British Columbia. Dr. Reidfunded by The Arthritis Society, B.C. Division. *Reprint address, The Arthritis Society, 895 14L lOth Ave., Vancouver, B.C. V5Z 1L7.
no history of rheumatic fever. At age 9 he was running poorly and his back was noted to have restricted mobility. Subsequently he developed pains in both knees, with an effusion and flexion deformity of the left knee. In May, 1975, the left knee was manipulated with the child under anesthesia. The anesthetist heard a cardiac murmur and the child was admitted for investigation. His father had psoriasis, but there was no other relevant family history. On examination his height was 138 cm and weight 30.5 kg. He was slightly pale and looked unwell, but had no evidence of iritis or rash. Peripheral pulse volume was increased and his blood pressure was 110/50, He had a visible left ventricular impulse outside the midclavicular line, with an associated heave, but no thrill. The first and second heart sounds were normal, with a Grade 2/6 ejection systolic murmur in the aortic area and neck, and a Grade 4/6 decrescendo diastolic murmur in the third and fourth left interspaces. There was no evidence of cardiac failure.
0022-3476/79/070078 +03500.30/0 9 1979 The C. V. Mosby Co.
Volume 95 Number 1
Brief clinical and laboratory observations
79
Fig. 1. M-mode '!sweep" from aortic root toward LV apex showing thickened echoes (arrowhead) superimposed over anterior mitral leaflet echo near the mitral ring.
Musculoskeletal examination showed a normal hip range but a marked reduction in mobility o f the lower spine, as evidenced by loss o f lumbar lordosis, flattening of the lumbar spine noted on attempted forward flexion, and reduction of forward flexion such that his finger tips reached only to the level of the tibial tubercles. There was wasting of the left quadriceps and calf muscles with a flexion deformity and effusion in his left knee, and a painful effusion o f his left ankle. There were also thickening and tenderness of the interphalangeal joint of his right thumb and metacarpophalangeal joint of his left index finger. Investigations. The hemoglobin was 11.0 gm/dl and the erythrocyte sedimentation rate 55 mm/hour. Results of tests for ANF, VDRL and RA Latex were all negative. The ASO titer was 50 Todd units/ml, and urinalysis was normal. HLA B-27 antigen was detected by tissue typing. Radiologically the sacroiliac joints were definitely abnormal: o n the iliac side of both joints there was sclerosis, which increased between 1974 and 1978, and there were erosions o f the right joint. Radiographs Of the spine were normal. Chest radiographs showed a moderately enlarged cardiac outline with a prominent left ventricular contour. The electrocardiogram showed sinus rhythm with normal conduction. A deep S in V o and tall R in V6 ( = 70 mm) suggested left
ventricular hypertrophy, but there was no evidence of strain. Echocardiography, using a 5 megahertz 6 mm diameter transducer, showed a normal aortic valve with a discrete central diastolic closure line. The aortic root was mildly dilated at 2.8 cm ( N = i.87 + 0.19) as was the left ventricle at 5.4 cm (N = 3,62 + 0.35) but contractility appeared normal. There was a diastolic flutter of both mitral valve leaflets and a thick echo complex related to the anterior mitral leaflet near the mitral ring (Fig. 1). Real time sector scans were obtained with a Picker Cardiac image r using a 5 megahertz 6 mm diameter short internal focus transducer. These showed thickening o f the anterior mitrat leaflet near the root of the aorta, identified as a "bump" !n Fig. 2. A linear echo anterior to the mitral valve was thought to be part of the chordal apparatus. Cardiac catheterization. Right and'retrograde left heart catheterization under sedation with meperidine revealed normal pressures and oxygen saturation values. There were no shunts on hydrogen ion potentiometric studies and there was a probe patent foramen ovale. Left ventricular angiograms in the LAO and RAO projections showed a dilated left ventricle, and a tricuspid aortic valve of which the right coronary cusp appeared more rigid. The mitral valve was competent and there appeared to be a
80
Brief clinical and laboratory observations
Fig. 2. Real time cross sectional echocardiogram in the sagittal plane lllust(ates thickening on anterior mitral leaflet at the base of the aorta, identified as "bump.!' AOR = Aortic root; AML = anterior mitral leaflet; IVS = interventricular septum; LA = left atriumi LV = left ventricle~ PML = post mitral leaflet. bump in the region of the anterior leaflet. The aortograms demonstrated normal coronary arteries and a moderately dilated root with aortic insufficiency (§ to +3) without cusp prolapse. DISCUSSION This patient has the cardinal features of ankylosing spondylitis, including pain, stiffness, and immobility of the back ~ with radiologic evidence of sacroiliitis. Ankylosing spondylitis has its m a x i m u m incidence in males between the ages of 20 and 40 years, 1 but a small series have been reported in children. 2-4 Ladd et al 2 noted that ankylosing spondylitis occurred in 7% of children seen for chronic arthritis, making this diagnosis unusual but not rare in children. In addition to the spine, our patient also had peripheraljo!nt !nvolvement, which is consistent with anky• losing spondylitis of early onset. Wilkinson and Bywaters 1 found the incidence of peripheral joint involvement in spondylitis With onset before age 20 was 40%, compared with 22% in those with onset after the age of 20. Like ankylosing sp0ndylitis, acquired aortic regurgitation is predominantly a disease of adult males. In childhood it is usually a sequel of acute rheumatic fever, and less commonly the result of bacterial endocarditis or associated with Marfan syndrome. In our patient the typical findings of aortic regurgitation with the joint manifestations of spondylitis made a c o m m o n etiology likely. Although rheumatic fever was suspected initially, the clinical and laboratory evidence did not substantiate this. The association between aortic insuff• and anky-
The Journal of Pediatrics July 1979 losing spondylitis was originally described by Bauer et al. 6 The prevalence of aortic insufficiency increases with the duration of the spondylitis, occurring in up to 10% of patients after 30 years, 6. 8. 9 but p a t i e n t s have been described in whom the lesion preceded the onset of spondylitis?. 7 Bulkley and Roberts 7 discussed the pathology of aortic regurgitation in ankylosing spondylitis. They described extension of the fibrous thickening of the wall of the aorta and its valve cusps onto the base of the anterior mitral leaflet, with a resultant ridge or " b u m p . " The extra echoes anterior to the mitral valve leaflet in Fig. 1 most likely represent this thickening, and the left ventricular anglogram and sector scan (Fig. 2) further support this interpretafion. The findings in our patient closely resemble those described in adults with ankylosing spondylitis and aortic insufficiency. The m a n a g e m e n t of this boy's cardiac disease is presently confined to prophylaxis against infective endocarditis. No restrictions of his activity are required because it is already quite limited by joint disease, which is managed with anti-inflammatory agents and physical therapy. The cardiac prognosis m children remains uncertain but it is reassuring to find that lack of progression ~ and a successful surgical repair have been reported in adults. TM Others are less optimistic, giving a 50% survival time o f seven years after the appearance of aortic insufficiency? The authors thank Dr. R. H. Hill for allowing them to report this case. REFERENCES
1
2. 3. 4. 5.
6.
7. 8. 9.
10.
Wilkinson M. and Bywaters EGL: Clinical features and course o f ankylosing spondylitis. Ann Rheum Dis 17:209. 1958. Ladd JR. Cassidy JT. and Martel W: Juvenile ankylosing spondylitis. Arthritis Rheum 14:579. 1971. Jacobs P: Ankylosing spondylitis in children and adolescents. Arch Dis Child 38:492. 1963. Schaller J, Bitnum S. and Wedgewood RJ: Ankylosing spondylitis with childhood onset. J PEDIATR74:505. 1969. Riley MJ, Ansell BM, and Bywaters EGL: Radiological manifestations of ankylosing spondylitis according to age at onset. Ann Rheum Dis 30:138, 1971. Bauer W. Clark WS. and Kulka JP: Aortitis and aortic endocarditis an unrecognized manifestation of rheumatoid arthritis. Ann Rheum Dis 10:470. 1951. Bulkley BH, and Roberts WC~ Ankylosing spondylitis in aortic regurgitation, Circulation 48:1014, 1973. Graham DC, and Smythe HA: The carditis and aortitis of ankylosing spondylitis. Bull Rheum Dis 9:171. 1958. Kinsella TD. Johnson LG. and Sutherland RI: Cardiovascular manifestations of ankylosing spondylitis. Can Med Assoc J 111:1309. 1974. Spitzer S, Peguero F. and Manson D: Rheumatoid spondylitis, aortic insufficiency and coronary artery disease. Chest 68:828, 1975.