- Email: [email protected]
Pregnancy and gout: A case report
PREGNANCY AND GOUT: A CASE REPORT A. FRIEDMAN, M.D., NEw YoRK, N.Y.
EMANUEL
AND WILLIAM
A.
LITTLE,
M.D '
(From the Sloane Hospital for Women, Columbia-Presbyterian Medical Center, and the Department of Obstetrics and Gynecology, Columbia University College of Physicians and Surgeons)
HE rarity with which gout is found among women, and more particularly among young women during their reproductive years, warrants the detailed reporting of cases associated with pregnancy. It is perhaps all the more important in consideration of the dire end results which may occur. A recent near-fatal case of gout in pregnancy, the only one of its kind known to have occurred at this institution, stimulated a search of the world literature in order to learn the experience of others. This review was all but fruitless, and despite special attention to reports dealing with gout in women,1 • :J. 5 • H , 12 • 15 • 16 only 2 published cases were diseovered. 6 • 10 It is generally agreed 2 • 14 that gout occurs very infrequently in females, less than 5 per cent of those afflicted being distaff. Sinee most are past the middle ~-ears of life when the disease becomes manifest, it is not unexpected that concurrent pregnancy is quite rare. Talbott14 writes, ''I am not familiar with a single example of hereditary tophaceous gout in a female who has produced offspring after the appearance of tophi.'' He elaims that there is a low fertility rate among married women with gout. 'J'hat this may be so cannot 1w ascertained, but one may assume a degree of Yoluntary sterility in association with advanced years and chronic debilitating disease.
T
The first of the 2 cases cited was reported in 19!5:1.6 lt involved a 28-year-old gravida with no familial history of gout whose first pregnancy in 1944 was eomplicated by pre-eclampsia. During the puerperium she developed uremia. Apparentl~- complete recovery followed in the ensuing year, and the patient did well until her next pregnancy in 1947. She again developed all the signs and symptoms of pre-eclampsia and, in addition, experienced progressively severe left flank pain. Delivery was uneventful. The flank pain persisted post partum, and symptoms of gouty arthritis developed. A year later a contracted left kidney was surgically removed, and the diagnosis of gout confirmed. Subsequently, tophi developed and a close correlation of exacerbations of the arthriti(' symptoms with menses was noted. 'l'he second case, reported in 1956,1° was that of a 27-year-old woman, also without a family history of gout, whose symptoms began at the age of 19. Radiographical confirmation of the diagnosis was obtained. During pregnancy in 1953, at the age of 24, remission of symptoms occurred. Rerum uric acid levels, however, remained slightly elevated. Delivery was uncomplieated. 913
914
FRU~DM.AN
ANil LlTTLE
Am. J. Ohst, & Gvnl'C Octnber. lq'k
Markedly increased uricemia was found during the first week post partum, bui there was no accompanying exacerbation of symptom>:. The latter recurred 11 months later and persisted intermittently thereafter. Review of the case histories of the 67 female patients with gout (preceding the case herein reported) under care at the Columbia-Presbyterian Medical Center since 1932 failed to reveal any associated pregnancies. All were older women, the large majority postmenopausal, the youngest 38 years of age. That pregnancies were not encountered in a group with this age dish'ibution is not difficult to understand. C. H. (No. 2i3971) was a 29-year-old whitP woman para JI, gravida V, who was referred here in the thirty-fourth week of pregnancy lweauRe of elevated blood pressure ani! headache. Pretibial P-ilema had been detected during tllf~ pr()viouR W<'Ak. The patient's first two pregnancies were uneventful; the last two, howev('r, tl•rminated spontaneously in abortion. Her medical history was ~ignifkant in that she had acute rheumatic f<'ver at the agte of 14 without sequela!'. During th<· past 6 .vears she hail a disorder involving both great toes, associated with pain and swelling. Two years previously this had been diagnosed as gout on the basis of blood urie acid levels and x-ray evidence of bony erosions. Both the patient's father and a si~tcr suff size of the uterus was smaller than that expected by dates. The fetus presented as Yertex; the fetal heart was audible in the right lower quadrant. Moderate pretibial and sacral edf'ma was noted. All deep t('ndon reflexes were hyperacth-e. Laboratory studies included: hemoglobin 13.9 Gm. per cent; leukocyte count 12,700 per cubic millimeter with normal differential; nonprotein nitrogen 61.6 and 72.8 mg. per cent; blood uric acid 8.3 and 8.6 mg. per cent; serum calcium 9.4 mg. per cent, phosphorous 3.9 mg. per cent, carbon dioxide 19.6 mEq. per liter, chloride 103.9 mEq. per liter, sodium 136.8 mEq. per liter, potassium 4.4 mEq. per liter; serum protein 6.8 per cent, albumin 4.9 per cent and globulin 1.9 per cent; alkaline phosphatase 4.7 units; cephalin flocculation and thymol turbidity negative. The Mazzini test was negative. An LE preparation was negative. TTrinalysis showed a specific gravity of 1.017, acid reaction, 1 plus albumin, and a few leukocytes and erythrocytes. The venous pressure was 150 mm. saline. A chest x-ray showed a slight cardiomegaly compatible with pregnancy; abdominal films showed a single fetus in cephalic presentation. The electrocardiogram was within normal limits. The patil!nt 's clinical course on a toxemia regimen of bed rest, salt restriction, and sedation rapidly deteriorated. She developed overt uremia with lethargy, uremic breath, and hyporefiexia. Her blood pressure remained in the 100 to 110 mm. Hg diastolic range. The urinary output fell precipitously. In view of the ominous portent of events, labor was inducecl by means of Pitocin infusion 4 days after admission. Following a 6¥.2 hour labor the patient was deliv'lred spontaneously of a 1,550 gram living female infant over an intact perineum. No anesthesia was necessary because of the patient's semicomatose state. The baby did remarkably well, and a~ of this writing is approaching ]H,r seeond birthday in excellent health. Post partum the patient exhibited rapid clinical improvement, despite disheartening laboratory evidence of continuing azotemia, the nonprotein nitrogen levels rising to 98.0 mg. per cent 5 days after delivery. In addition, arthritic symptoms recurr<'d. All signs and symptoms slowly diminished, however, over the next several weeks. Further laboratory investigation yielded phenolsulfonphthalein excretion o:f 80 per cent, catechol-amine excretion
\ ,,,lilllt' if) :\ ll!llht'l
4
PREGNANCY AND OOl''l'
wi.thiu nonual limits, and basal metabolic rate minus 9 per cent. The patient was discharge
It \Y:tS felt that this episode had represented an acute uremic condition secondary to gouty nephritis with probable superimposed severe pre-eclampsia. The patient was warne
Comment A definitive statement as to the potential interaction of gout and pregnancy cannot be made on the basis of the 3 cases cited. Furthermore, the second case 10 was apparently quite mild and contributed very little to our understanding of this problem. In so far as the fertility of affected women is concerned, it has been pointed out that Y<'ry few acquire their disease at a period in life when the reproductive potential is heing utilized. Where the disease· is manifested early, as in the cases reported, pregnancy seems to occur with normal frequency. These i3 ,,·omen had a total of 9 pregnancies, resulting in 5 living children, 2 spontaneous abortions, and one therapeutic interruption. Indeed, the last mentioned was conceived as a result of failure of contraception. It appears therefore. that sterility is not directly attributable to gout. 'l'he clinical course of gout may be related to concurrent pregnancy. In 2 of the: patients the pre-eclampsia syndrome was notable. rremia, albeii reversible, followed. Although thP symptoms of arthritis largely r-mhsided during the pregnancies in question, post partum exacerbations occurred. One may speculate on the possible mutually antagonistie effects which two disorders, gout and pre-eclampsia, both assoeiated with nricemia, have upon each other. .A recent report 4 suggests that uricemia in toxemia is a result of increased renal tubular reabsorption and occurs in the absence of other renal function disturbances. In gout, on the other hand, most agree11 • 13 that deposits of mate crystals in the renal pyramids produce compression of the collecting tubules with subsequent atrophy of the nephron. In combination, functional
916
l<'RIEDMAN AND Ll'l'TLE
\m.
J.
()Lst. & (;yilt'~
lktuber,
l9~t'
renal insufficiency may result, ending in uremia. The pathophysiological changes of toxemia elevate serum uric acid levels, thereby augmenting the metaholie uric acid disorder characteristic of gout. It seems reasonable, therefore, to expect clinical antagonism between gout and toxemia. On the basis of observations made here and elsewhere, one may postulate a relationship between exacerbation of the symptoms of gout and estrogen withdrawal. It is known, for example, that symptoms of gout seldom manifest themselves until during or after the mcnopause. 6 In premenopausal patients, co-menstrual attacks are not at all uncommon. 8 Two of the cases reviewed in this report present further suggestive evidence, in that exacerbations occurred postpartum. The theory, however, is not supported by the noteworthy recrudescence of symptoms in the last pregnancy of the third patient. The relationships here arc at best cloudy. It is hoped that wider interest in these problems will result from this presentation. Summary
The extremely rare association of gout and pregnancy has been examined by the presentation of a case report and summarization of the 2 other cases which have appeared in the literature to date. The possible interrelationship of gout and pre-eclampsia has been discussed, with the tentative conclusion reached that the two conditions are mutually antagonistic. The role of estrogen withdrawal in gouty exacerbations has been implied and, although not clear-cut, a causal relationship is felt to exist. References 1. Bartfield, H.: J. A. M. A. 154: 335, 1954. 2. Cecil, R. L. and Loeb, R. F.: A Textbook of Medicine. Philadelphia, 1951, W. B. Saunders Company. 3. Claiborne, T. S.: J. A. M. A. 115: 38, 1940. 4. Czaczkes, W. J., ffilmann, T. D., and Sadowsky, E.: J. Lab. & Olin. Med. 51: 224, 1958. 5. FranC}on, F., FranC}on, J., and Faidherbe, P.: Rev. du rhum. 22: 137, 1955. 6. Greenhut, I. J., Silver, R. A., and Campbell, J. A.: Radiology 60: 257, 1953. 7. Halsted, J. A.: New England J. Med. 218: 723, 1938. 8. Hill, L. C.: Lancet 1: 826, 1938. 9. Kinell, J., and Haden, R.: M. Clin. North America 24: 429, 19-W. 10. Mace, B. E. W.: Revue du rhum. 23: 156, 1956. 11. Modern, F. W. S., and Meister, L: M. Olin. North America 36: 941, 1952. 12. Perlman, L., Bernstein, A., Maslow, W. C., and Scatliff, J. H.: J. A. M. A. 151: 726, 1953. 13. Sokoloff, L.: Metabolism 6: 230, 1957. 14. Talbott, J. H.: Gout, ed. 2 New York, 1957, Grune & Stratton. 15. Thomson, F. G.: Brit. J. Rheumat. 1: 25, 1938. 16. Wolfson, W. Q. et al: J. Olin. Endocrinol. 9: 497, 1949.
EMANUEL
AND WILLIAM
A.
LITTLE,
M.D '
(From the Sloane Hospital for Women, Columbia-Presbyterian Medical Center, and the Department of Obstetrics and Gynecology, Columbia University College of Physicians and Surgeons)
HE rarity with which gout is found among women, and more particularly among young women during their reproductive years, warrants the detailed reporting of cases associated with pregnancy. It is perhaps all the more important in consideration of the dire end results which may occur. A recent near-fatal case of gout in pregnancy, the only one of its kind known to have occurred at this institution, stimulated a search of the world literature in order to learn the experience of others. This review was all but fruitless, and despite special attention to reports dealing with gout in women,1 • :J. 5 • H , 12 • 15 • 16 only 2 published cases were diseovered. 6 • 10 It is generally agreed 2 • 14 that gout occurs very infrequently in females, less than 5 per cent of those afflicted being distaff. Sinee most are past the middle ~-ears of life when the disease becomes manifest, it is not unexpected that concurrent pregnancy is quite rare. Talbott14 writes, ''I am not familiar with a single example of hereditary tophaceous gout in a female who has produced offspring after the appearance of tophi.'' He elaims that there is a low fertility rate among married women with gout. 'J'hat this may be so cannot 1w ascertained, but one may assume a degree of Yoluntary sterility in association with advanced years and chronic debilitating disease.
T
The first of the 2 cases cited was reported in 19!5:1.6 lt involved a 28-year-old gravida with no familial history of gout whose first pregnancy in 1944 was eomplicated by pre-eclampsia. During the puerperium she developed uremia. Apparentl~- complete recovery followed in the ensuing year, and the patient did well until her next pregnancy in 1947. She again developed all the signs and symptoms of pre-eclampsia and, in addition, experienced progressively severe left flank pain. Delivery was uneventful. The flank pain persisted post partum, and symptoms of gouty arthritis developed. A year later a contracted left kidney was surgically removed, and the diagnosis of gout confirmed. Subsequently, tophi developed and a close correlation of exacerbations of the arthriti(' symptoms with menses was noted. 'l'he second case, reported in 1956,1° was that of a 27-year-old woman, also without a family history of gout, whose symptoms began at the age of 19. Radiographical confirmation of the diagnosis was obtained. During pregnancy in 1953, at the age of 24, remission of symptoms occurred. Rerum uric acid levels, however, remained slightly elevated. Delivery was uncomplieated. 913
914
FRU~DM.AN
ANil LlTTLE
Am. J. Ohst, & Gvnl'C Octnber. lq'k
Markedly increased uricemia was found during the first week post partum, bui there was no accompanying exacerbation of symptom>:. The latter recurred 11 months later and persisted intermittently thereafter. Review of the case histories of the 67 female patients with gout (preceding the case herein reported) under care at the Columbia-Presbyterian Medical Center since 1932 failed to reveal any associated pregnancies. All were older women, the large majority postmenopausal, the youngest 38 years of age. That pregnancies were not encountered in a group with this age dish'ibution is not difficult to understand. C. H. (No. 2i3971) was a 29-year-old whitP woman para JI, gravida V, who was referred here in the thirty-fourth week of pregnancy lweauRe of elevated blood pressure ani! headache. Pretibial P-ilema had been detected during tllf~ pr()viouR W<'Ak. The patient's first two pregnancies were uneventful; the last two, howev('r, tl•rminated spontaneously in abortion. Her medical history was ~ignifkant in that she had acute rheumatic f<'ver at the agte of 14 without sequela!'. During th<· past 6 .vears she hail a disorder involving both great toes, associated with pain and swelling. Two years previously this had been diagnosed as gout on the basis of blood urie acid levels and x-ray evidence of bony erosions. Both the patient's father and a si~tcr suff
\ ,,,lilllt' if) :\ ll!llht'l
4
PREGNANCY AND OOl''l'
wi.thiu nonual limits, and basal metabolic rate minus 9 per cent. The patient was discharge
It \Y:tS felt that this episode had represented an acute uremic condition secondary to gouty nephritis with probable superimposed severe pre-eclampsia. The patient was warne
Comment A definitive statement as to the potential interaction of gout and pregnancy cannot be made on the basis of the 3 cases cited. Furthermore, the second case 10 was apparently quite mild and contributed very little to our understanding of this problem. In so far as the fertility of affected women is concerned, it has been pointed out that Y<'ry few acquire their disease at a period in life when the reproductive potential is heing utilized. Where the disease· is manifested early, as in the cases reported, pregnancy seems to occur with normal frequency. These i3 ,,·omen had a total of 9 pregnancies, resulting in 5 living children, 2 spontaneous abortions, and one therapeutic interruption. Indeed, the last mentioned was conceived as a result of failure of contraception. It appears therefore. that sterility is not directly attributable to gout. 'l'he clinical course of gout may be related to concurrent pregnancy. In 2 of the: patients the pre-eclampsia syndrome was notable. rremia, albeii reversible, followed. Although thP symptoms of arthritis largely r-mhsided during the pregnancies in question, post partum exacerbations occurred. One may speculate on the possible mutually antagonistie effects which two disorders, gout and pre-eclampsia, both assoeiated with nricemia, have upon each other. .A recent report 4 suggests that uricemia in toxemia is a result of increased renal tubular reabsorption and occurs in the absence of other renal function disturbances. In gout, on the other hand, most agree11 • 13 that deposits of mate crystals in the renal pyramids produce compression of the collecting tubules with subsequent atrophy of the nephron. In combination, functional
916
l<'RIEDMAN AND Ll'l'TLE
\m.
J.
()Lst. & (;yilt'~
lktuber,
l9~t'
renal insufficiency may result, ending in uremia. The pathophysiological changes of toxemia elevate serum uric acid levels, thereby augmenting the metaholie uric acid disorder characteristic of gout. It seems reasonable, therefore, to expect clinical antagonism between gout and toxemia. On the basis of observations made here and elsewhere, one may postulate a relationship between exacerbation of the symptoms of gout and estrogen withdrawal. It is known, for example, that symptoms of gout seldom manifest themselves until during or after the mcnopause. 6 In premenopausal patients, co-menstrual attacks are not at all uncommon. 8 Two of the cases reviewed in this report present further suggestive evidence, in that exacerbations occurred postpartum. The theory, however, is not supported by the noteworthy recrudescence of symptoms in the last pregnancy of the third patient. The relationships here arc at best cloudy. It is hoped that wider interest in these problems will result from this presentation. Summary
The extremely rare association of gout and pregnancy has been examined by the presentation of a case report and summarization of the 2 other cases which have appeared in the literature to date. The possible interrelationship of gout and pre-eclampsia has been discussed, with the tentative conclusion reached that the two conditions are mutually antagonistic. The role of estrogen withdrawal in gouty exacerbations has been implied and, although not clear-cut, a causal relationship is felt to exist. References 1. Bartfield, H.: J. A. M. A. 154: 335, 1954. 2. Cecil, R. L. and Loeb, R. F.: A Textbook of Medicine. Philadelphia, 1951, W. B. Saunders Company. 3. Claiborne, T. S.: J. A. M. A. 115: 38, 1940. 4. Czaczkes, W. J., ffilmann, T. D., and Sadowsky, E.: J. Lab. & Olin. Med. 51: 224, 1958. 5. FranC}on, F., FranC}on, J., and Faidherbe, P.: Rev. du rhum. 22: 137, 1955. 6. Greenhut, I. J., Silver, R. A., and Campbell, J. A.: Radiology 60: 257, 1953. 7. Halsted, J. A.: New England J. Med. 218: 723, 1938. 8. Hill, L. C.: Lancet 1: 826, 1938. 9. Kinell, J., and Haden, R.: M. Clin. North America 24: 429, 19-W. 10. Mace, B. E. W.: Revue du rhum. 23: 156, 1956. 11. Modern, F. W. S., and Meister, L: M. Olin. North America 36: 941, 1952. 12. Perlman, L., Bernstein, A., Maslow, W. C., and Scatliff, J. H.: J. A. M. A. 151: 726, 1953. 13. Sokoloff, L.: Metabolism 6: 230, 1957. 14. Talbott, J. H.: Gout, ed. 2 New York, 1957, Grune & Stratton. 15. Thomson, F. G.: Brit. J. Rheumat. 1: 25, 1938. 16. Wolfson, W. Q. et al: J. Olin. Endocrinol. 9: 497, 1949.