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A case report of the use of combined doca andascorbic acid in a 12-year-old child with rheumatoid arthritis
A CASE R E P O R T OF T t I E U S E OF C O M B I N E D D O C A A N D A S C O R B I C A C I D I N A 12-YEAR-OLD C H I L D W I T H RHEUMATOID ARTHRITIS
BEATRICEBERGMAN,M.D., AND FRANK R. I{INBERGER,M.D. NEW YOR~, N. Y. N O P P O R T U N I T Y to appraise the new t r e a t m e n t for r h e u m a t o i d a r t h r i t i s suggested b y Lewin a n d Wass6n 1 p r e s e n t e d itself with the admission of a 12 89 female to the P e d i a t r i c Service of the U n i v e r s i t y Hospital. A f t e r a comprehensive s u r v e y of the pediatric l i t e r a t u r e we have been unable to find a n y reference to the use of desoxycorticosterone acetate and v i t a m i n C in the treatment of rheumatic arthritis in children to date. Widespread interest has been stimulated in the therapy of rheumatic arthritis by the publications of Hench and collaborators 2 in the successful use of ACTI-I and cortisone. Since ACTH and cortisone are diffleu]t to obtain, expensive, and often attended with toxicity, we felt that this case afforded us the opportunity to evaluate the desoxyeortieosterone acetate and vitamin C method of therapy. CASE
HISTORY
The patient is a 121~-year-old white female who was admitted to the Babies' Ward of the University Hospital, New York University-Bellevue Medical Center on Jan. 30, ]950, with the chief complaint of pain in the neck and hands for three months' duration and swelling of the ankles intermittently for a period of three years. Her past history revealed that she had had the usual childhood diseases. At the age of 9 years a questionable diagnosis of rheumatic fever was made, for which the child spent three months in bed. The present illness had its onset three months prior to admission to the hospital when she developed pains in her wrists and fingers. Later these symptoms spread to involve her neck. She was hospitalized at another institution where a diagnosis of arthritis was made. So far as we know no form of treatment was instituted, and for the past two months the signs and symptoms referable to the parts mentioned have progressed. Physical examination revealed a poorly nourished, depressed, and anhappy white female who was very cooperative and friendly. Weight was 671/2 pounds, pulse 98, respirations 20, and temperature 98.6 ~ F. Except for the following positive points, the remainder of the physical examination was essentially negative. Neck: The neck is held in a slightly flexed, strained position. Flexion can be accomplished with ease. Extension is limited to about 30 degrees; rotation to the right limited to about 30 degrees and to the left 50 degrees. Hands: There are swellings of both the proximal and distal interphalangeal joints that are nontender to palpation. Definite crepitation is present on passive movement of the affected joints. From Feb. 8 through March 10, 1950, she received twenty-nine physiotherapy treatments consisting of tank treatments with motion of the involved joints. Although slightly improved subjectively during this period there was From the Department of Pediatrics of the IJniversity School, New York University-Bellevue Medical Center. 774
Hospital
and
Post
Graduate
Medical
BERGMAN AND KINBERGER:
775
RHEUhiATOID ARTHRITIS
no real objective i m p r o v e m e n t according to the physiotherapist. Because of the u n a p p r e e i a b l e results thus obtained it was decided to institute t h e r a p y s u g g e s t e d b y L e w i n and Wass~n. ~ P h y s i o t h e r a p y was discontinued. The various p r o c e d u r e s listed in Table I were done p r i o r to t h e r a p y . TABLE
CBC
WEIGHT
BLOOD
(POUNDS)
PRESSURE
Before Treatment R.B.C. 4.5 rail. 68 ttb. 12.5 Gm. W.B.C. 5,900 P 75 L S2 IVI
3/8/50 118/78
I
SODIUH
POTASSIUH
3/8/50 121.3 meq.
3/8/50 4.2 meq.
URINARY SUGAR
Neg.
SEDIMENTATION RATE
BLOOD CHEMISTRY
Average Uric acid 1.8 rag. 8 % m m . / h r . I n o r g a n i c phosp h o r u s 3.2 rag.
%
3
Total mg.
caleium %
1].2
Alkaline phosp h a t a s e 4.9 Bodansky units
During Treatment W i t h D o c a and Ascorbic Acid W.B.C. 4,850 68 3/]0/50 P 53 ]00/80 L 33 691/2 3 / 1 1 / 5 0 1Y[ 14 128/98 67~ 3/]5/50 3/15/50 108-118 129 meq. 5.7 meq. 70 70
3/7/50 8 mm./hr. Xeg.
3/16/50 Neg.
The m e t h o d of t r e a t m e n t was as follows : An i n t r a m u s c u l a r injection of 2.5 mg. of desoxycorticosterone acetate ( P e r c o r t e n ) ~:' was given and then followed in five minutes b y an i n t r a v e n o u s injection of 500 rag. of ascorbic acid in 1 c.e. of saline. I n addition, the child was offered a low sodium diet to avoid a n y possible effect of Doca on salt and w a t e r retention. RESULTS
Within ten minutes after the intravenous injection of ascorbic acid marked beneficial effects were noted. The child appeared more animated and volunteered the information that her joints felt less stiff and that she could move them more freely. Measurementst of the affected joints made ten minutes and four hours after the treatment were compared with measurements made directly before treatment (Table II). All of these measurements were performed by one of us (F. R. K.). Treatment was repeated twenty-four and ninety-six hours after the initial injection. The results are also recorded in Table If. It can be seen that there was definite increase of range of motion-compare italic figures in Table II. The sedimentation rate showed no change, no electrolyte disturbance, no urinary sugar. There was no evidence of edema or gain in weight. In short, none of the toxic effects observed with ACTII and cortisone were noted. Since we were unable to continue treatments in the hospital because the patient lived at a great distance from the hospital and because of her anxiety to get home, the child was sent home on Pregnenolone,$ s 100 mR. three times daily. *One-half of the adult dose recommended by Lewin and Wass~n was decided upon because the optimum dose in children had not been established. tMeasurements were made by means of an a r t h r o m e t e r (Whittier). $Wyeth Incorporated, Philadelphia, Pa.
776
THE JOURNAL OF PEDIATRICS TABLE
II.
I~ESULTS
3/9/50 BEFOaE
OBTAINED
~IN.
WIT~I
BOCA
4 HR., ]5 MIN.
AND
3/10/50
ASCORBIC
3/13/50
ACID
3/]4/50 BEFORE I AFTER
RIGHT
Wrist
58
65
66
65
59
60
69
Thumb
Proximal Distal
57 23
54 29
54 36
56 27
60 24
52 23
60 30
Index
Proximal Distal
66 25
73 34
72 36
8:1 29
67 27
75 25
76 28
Middle
Proximal Distal
55 40
65 52
68 52
66 51
65 44
72
66
40
5~
Ring
Proximal Distal
68 34
78 43
82 48
85 47
76 40
85 45
84
Little
Proximal Distal
70 36
87 42
77 45
84 43
83 30
77 39
80 45
63
72
72
72
73
66
78
Proximal Distal
51 32
51 47
53 43
55 56
53 53
55 44
d6
Proximal Distal
51
34
68 30
63 34
69 35
69 32
70 28
75 29
Proximal Distal
62 52
72 48
73 54
70 48
77 45
72 49
49
l~ing
Proximal Distal
81 45
83 46
83 41
87 44
85 39
83 41
90 45
Little
Proximal Distal
66 49
66 52
63 55
78 50
63 54
65
73 62
43
LEFT
Wrist Thumb Index Middle
Note:
Measurements
are in angle
58
54
78
of flexion.
SUMI~IARu
A child with rheumatic arthritis was treated with Doea and ascorbic acid. I t might be well to mention that this treatment in adults has been the subject of controversy, 4, 5, 6 Objective measurements which were recorded indicate that there was i m p r o v e m e n t in this case, w h i c h was maintained with only slight regression. We are aware of the fact that definite conclusions cannot be d r a w n on the results obtained with this type of t r e a t m e n t in one case but our results are encouraging. I t is hoped t h a t this case report will stimulate f u r t h e r interest in investigation o2 this t y p e o~ t h e r a p y in order t h a t it m a y be more fully evaluated. Speculation arises as to whether the effects were due to the combined Doca and ascorbic acid, or to the ascorbic acid t h e r a p y aloneJ W e wish to t h a n k Dr. Charles V a r g a a n d Miss S o n j a I t : r a m a r s k y f o r t h e i r a s i s t a n c e in t h e p r e p a r a t i o n of t h i s p a p e r . REFERENCES 1. L e w i n , E., a n d W a s s 6 n , E.: E f f e c t of C o m b i n e d I n j e c t i o n s of D e o x y c o r t o n e A c e t a t e a n d A s c o r b i c A c i d on R h e u m a t o i d A r t h r i t i s , L a n c e t 2: 993, 1949. 2. I t e n c h , P. S., K e n d a l l , E. C., S]ocumb, C. H., a n d P o l l e y , H. 1~.: E f f e c t of H o r m o n e of A d r e n a l C o r t e x ( 1 7 - h y d r o x y - l l - d e h y d r o c o r t i c o s t e r o n e : . C o m p o u n d E ) a n d of P i t u i t a r y A d r e n o c o r t i c o t r o p i c I t o r m o n e on R h e u m a t o i d A r t h r i t i s : P r e l i m i n a r y R e p o r t , Proc. S t a f f M e e t i n g , M a y o Clin. 24: 181, 1949:
BERG~IAN AND I~INBERGER:
RHEUMATOID ARTHRITIS
777
3. l~reeman, H., Pincus, G., Johnson, C. W., Bachrach, S., McCabe, G. E., and 1ViacGilpin, H.: Therapeutic Efficacy of A~-Pregnenoione in Rheumatoid A r t h r i t i s , J. A. M. A. 142: 1124, 1950. 4. Hartfall~ S. J., and Harris~ R.: I)eoxyeortone A c e t a t e and Ascorbic Acid in R h e u m a t o i d A r t h r i t i s , L a n c e t 2: 1202, 1949. 5. Loxton, G. E., and LeYay, D.: Deoxycortone A c e t a t e and Ascorbic Acid in Rheumatoid A r t h r i t i s , L a n c e t 2: 1204, 1949. 6. Zondek, It.: Deoxycortone A c e t a t e and Ascorbic Acid in Anky]osing Spondylitis, L a n c e t 1: 517, 1950. 7. ~:~r B. F.~ Warren, J. E., Patterson~ P. R., a n d Lehmus, H. J.: A n t i r h e u m a t i c Act i v i t y of Ascorbic Acid in Large Doses: P r e l i m i n a r y Observations on Seven P a t i e n t s W i t h R h e u m a t i c Fever, New E n g l a n d J. Med. 242: 614, 1950.
BEATRICEBERGMAN,M.D., AND FRANK R. I{INBERGER,M.D. NEW YOR~, N. Y. N O P P O R T U N I T Y to appraise the new t r e a t m e n t for r h e u m a t o i d a r t h r i t i s suggested b y Lewin a n d Wass6n 1 p r e s e n t e d itself with the admission of a 12 89 female to the P e d i a t r i c Service of the U n i v e r s i t y Hospital. A f t e r a comprehensive s u r v e y of the pediatric l i t e r a t u r e we have been unable to find a n y reference to the use of desoxycorticosterone acetate and v i t a m i n C in the treatment of rheumatic arthritis in children to date. Widespread interest has been stimulated in the therapy of rheumatic arthritis by the publications of Hench and collaborators 2 in the successful use of ACTI-I and cortisone. Since ACTH and cortisone are diffleu]t to obtain, expensive, and often attended with toxicity, we felt that this case afforded us the opportunity to evaluate the desoxyeortieosterone acetate and vitamin C method of therapy. CASE
HISTORY
The patient is a 121~-year-old white female who was admitted to the Babies' Ward of the University Hospital, New York University-Bellevue Medical Center on Jan. 30, ]950, with the chief complaint of pain in the neck and hands for three months' duration and swelling of the ankles intermittently for a period of three years. Her past history revealed that she had had the usual childhood diseases. At the age of 9 years a questionable diagnosis of rheumatic fever was made, for which the child spent three months in bed. The present illness had its onset three months prior to admission to the hospital when she developed pains in her wrists and fingers. Later these symptoms spread to involve her neck. She was hospitalized at another institution where a diagnosis of arthritis was made. So far as we know no form of treatment was instituted, and for the past two months the signs and symptoms referable to the parts mentioned have progressed. Physical examination revealed a poorly nourished, depressed, and anhappy white female who was very cooperative and friendly. Weight was 671/2 pounds, pulse 98, respirations 20, and temperature 98.6 ~ F. Except for the following positive points, the remainder of the physical examination was essentially negative. Neck: The neck is held in a slightly flexed, strained position. Flexion can be accomplished with ease. Extension is limited to about 30 degrees; rotation to the right limited to about 30 degrees and to the left 50 degrees. Hands: There are swellings of both the proximal and distal interphalangeal joints that are nontender to palpation. Definite crepitation is present on passive movement of the affected joints. From Feb. 8 through March 10, 1950, she received twenty-nine physiotherapy treatments consisting of tank treatments with motion of the involved joints. Although slightly improved subjectively during this period there was From the Department of Pediatrics of the IJniversity School, New York University-Bellevue Medical Center. 774
Hospital
and
Post
Graduate
Medical
BERGMAN AND KINBERGER:
775
RHEUhiATOID ARTHRITIS
no real objective i m p r o v e m e n t according to the physiotherapist. Because of the u n a p p r e e i a b l e results thus obtained it was decided to institute t h e r a p y s u g g e s t e d b y L e w i n and Wass~n. ~ P h y s i o t h e r a p y was discontinued. The various p r o c e d u r e s listed in Table I were done p r i o r to t h e r a p y . TABLE
CBC
WEIGHT
BLOOD
(POUNDS)
PRESSURE
Before Treatment R.B.C. 4.5 rail. 68 ttb. 12.5 Gm. W.B.C. 5,900 P 75 L S2 IVI
3/8/50 118/78
I
SODIUH
POTASSIUH
3/8/50 121.3 meq.
3/8/50 4.2 meq.
URINARY SUGAR
Neg.
SEDIMENTATION RATE
BLOOD CHEMISTRY
Average Uric acid 1.8 rag. 8 % m m . / h r . I n o r g a n i c phosp h o r u s 3.2 rag.
%
3
Total mg.
caleium %
1].2
Alkaline phosp h a t a s e 4.9 Bodansky units
During Treatment W i t h D o c a and Ascorbic Acid W.B.C. 4,850 68 3/]0/50 P 53 ]00/80 L 33 691/2 3 / 1 1 / 5 0 1Y[ 14 128/98 67~ 3/]5/50 3/15/50 108-118 129 meq. 5.7 meq. 70 70
3/7/50 8 mm./hr. Xeg.
3/16/50 Neg.
The m e t h o d of t r e a t m e n t was as follows : An i n t r a m u s c u l a r injection of 2.5 mg. of desoxycorticosterone acetate ( P e r c o r t e n ) ~:' was given and then followed in five minutes b y an i n t r a v e n o u s injection of 500 rag. of ascorbic acid in 1 c.e. of saline. I n addition, the child was offered a low sodium diet to avoid a n y possible effect of Doca on salt and w a t e r retention. RESULTS
Within ten minutes after the intravenous injection of ascorbic acid marked beneficial effects were noted. The child appeared more animated and volunteered the information that her joints felt less stiff and that she could move them more freely. Measurementst of the affected joints made ten minutes and four hours after the treatment were compared with measurements made directly before treatment (Table II). All of these measurements were performed by one of us (F. R. K.). Treatment was repeated twenty-four and ninety-six hours after the initial injection. The results are also recorded in Table If. It can be seen that there was definite increase of range of motion-compare italic figures in Table II. The sedimentation rate showed no change, no electrolyte disturbance, no urinary sugar. There was no evidence of edema or gain in weight. In short, none of the toxic effects observed with ACTII and cortisone were noted. Since we were unable to continue treatments in the hospital because the patient lived at a great distance from the hospital and because of her anxiety to get home, the child was sent home on Pregnenolone,$ s 100 mR. three times daily. *One-half of the adult dose recommended by Lewin and Wass~n was decided upon because the optimum dose in children had not been established. tMeasurements were made by means of an a r t h r o m e t e r (Whittier). $Wyeth Incorporated, Philadelphia, Pa.
776
THE JOURNAL OF PEDIATRICS TABLE
II.
I~ESULTS
3/9/50 BEFOaE
OBTAINED
~IN.
WIT~I
BOCA
4 HR., ]5 MIN.
AND
3/10/50
ASCORBIC
3/13/50
ACID
3/]4/50 BEFORE I AFTER
RIGHT
Wrist
58
65
66
65
59
60
69
Thumb
Proximal Distal
57 23
54 29
54 36
56 27
60 24
52 23
60 30
Index
Proximal Distal
66 25
73 34
72 36
8:1 29
67 27
75 25
76 28
Middle
Proximal Distal
55 40
65 52
68 52
66 51
65 44
72
66
40
5~
Ring
Proximal Distal
68 34
78 43
82 48
85 47
76 40
85 45
84
Little
Proximal Distal
70 36
87 42
77 45
84 43
83 30
77 39
80 45
63
72
72
72
73
66
78
Proximal Distal
51 32
51 47
53 43
55 56
53 53
55 44
d6
Proximal Distal
51
34
68 30
63 34
69 35
69 32
70 28
75 29
Proximal Distal
62 52
72 48
73 54
70 48
77 45
72 49
49
l~ing
Proximal Distal
81 45
83 46
83 41
87 44
85 39
83 41
90 45
Little
Proximal Distal
66 49
66 52
63 55
78 50
63 54
65
73 62
43
LEFT
Wrist Thumb Index Middle
Note:
Measurements
are in angle
58
54
78
of flexion.
SUMI~IARu
A child with rheumatic arthritis was treated with Doea and ascorbic acid. I t might be well to mention that this treatment in adults has been the subject of controversy, 4, 5, 6 Objective measurements which were recorded indicate that there was i m p r o v e m e n t in this case, w h i c h was maintained with only slight regression. We are aware of the fact that definite conclusions cannot be d r a w n on the results obtained with this type of t r e a t m e n t in one case but our results are encouraging. I t is hoped t h a t this case report will stimulate f u r t h e r interest in investigation o2 this t y p e o~ t h e r a p y in order t h a t it m a y be more fully evaluated. Speculation arises as to whether the effects were due to the combined Doca and ascorbic acid, or to the ascorbic acid t h e r a p y aloneJ W e wish to t h a n k Dr. Charles V a r g a a n d Miss S o n j a I t : r a m a r s k y f o r t h e i r a s i s t a n c e in t h e p r e p a r a t i o n of t h i s p a p e r . REFERENCES 1. L e w i n , E., a n d W a s s 6 n , E.: E f f e c t of C o m b i n e d I n j e c t i o n s of D e o x y c o r t o n e A c e t a t e a n d A s c o r b i c A c i d on R h e u m a t o i d A r t h r i t i s , L a n c e t 2: 993, 1949. 2. I t e n c h , P. S., K e n d a l l , E. C., S]ocumb, C. H., a n d P o l l e y , H. 1~.: E f f e c t of H o r m o n e of A d r e n a l C o r t e x ( 1 7 - h y d r o x y - l l - d e h y d r o c o r t i c o s t e r o n e : . C o m p o u n d E ) a n d of P i t u i t a r y A d r e n o c o r t i c o t r o p i c I t o r m o n e on R h e u m a t o i d A r t h r i t i s : P r e l i m i n a r y R e p o r t , Proc. S t a f f M e e t i n g , M a y o Clin. 24: 181, 1949:
BERG~IAN AND I~INBERGER:
RHEUMATOID ARTHRITIS
777
3. l~reeman, H., Pincus, G., Johnson, C. W., Bachrach, S., McCabe, G. E., and 1ViacGilpin, H.: Therapeutic Efficacy of A~-Pregnenoione in Rheumatoid A r t h r i t i s , J. A. M. A. 142: 1124, 1950. 4. Hartfall~ S. J., and Harris~ R.: I)eoxyeortone A c e t a t e and Ascorbic Acid in R h e u m a t o i d A r t h r i t i s , L a n c e t 2: 1202, 1949. 5. Loxton, G. E., and LeYay, D.: Deoxycortone A c e t a t e and Ascorbic Acid in Rheumatoid A r t h r i t i s , L a n c e t 2: 1204, 1949. 6. Zondek, It.: Deoxycortone A c e t a t e and Ascorbic Acid in Anky]osing Spondylitis, L a n c e t 1: 517, 1950. 7. ~:~r B. F.~ Warren, J. E., Patterson~ P. R., a n d Lehmus, H. J.: A n t i r h e u m a t i c Act i v i t y of Ascorbic Acid in Large Doses: P r e l i m i n a r y Observations on Seven P a t i e n t s W i t h R h e u m a t i c Fever, New E n g l a n d J. Med. 242: 614, 1950.