Gouty arthritis in the black race

Gouty Arthritis in the Black Race By John H. Talbott,

Norman

Gottlieb,

Peter Grendelmeier,

and Emilio Rodriguez

P

has been given to the deROBABLY TOO LITTLE ATTENTION velopment of gouty arthritis among members of the black race, with the implication that the disease is uncommon, in contrast to the incidence among whites. Until recent years, when a black was seen with clinical gout, this finding was looked upon primarily as a medical curiosity. Thus, in 1940, Hench’ expressed the generally held impression at that time that gout was rare among native races, a view reinforced as recently as 1956 in a highly reputable textbook of medicine: “Gout is much commoner among certain races. . . . It is very uncommon among native races.“2 We have not prepared this review to claim the opposite, i.e., that gout is very common among native races, but it seems evident that the incidence of gout among the blacks may not be fully appreciated. If this is valid, the diagnosis of gout may be missed at the time of the initial bout of acute gouty arthritis, or worse still, the suspicion of gout may be delayed for some period of time, thereby depriving the patient of antigout medication which is thoroughly satisfactory in the relief of both acute and chronic symptoms. Since 65 black patients with gout were seen by us over a period of less than 1 yr, this report summarizes several of the specific aspects of this group. REVIEW

OF REPORTED

CASES

One of the first examples of a black patient with gout in Western medicine was a South African Negro reported by Andrew in the Edinburgh Medical and Surgical Journal of 1807.3 In 1904, Futcher, one of the early Americans in this century to be concerned with gout, reported 59 cases of gouty arthritis from Baltimore, of which three were listed as nonwhites, without further identification.4 These could well have been blacks because of the number of blacks in Baltimore. In 1920, Williamson reported two cases of gout in a series of 116 patients with gout seen at the Cook County Hospital in Chicago. No mention was made of sex, hence we can conclude that most likely they were males.5 In 1941, Cohen of Philadelphia reported three black brothers with gout and considered this ethnic identification unusual. The first brother had his initial attack of gouty arthritis at the age of 12, which subsequently progressed to involve

From the Arthritis Division, Department of Medicine, School of Medicine, University of Miami, Miami, Fla. 33152. John H. Talbott, M.D.: Clinical Professor of Medicine, Arthritis Division, Department of Medicine, School of Medicine. University of Miami, Miami, Fla. 33152. Norman Gottlieb, M.D.: Associate Professor of Medicine, Arthritis Division, Departmenr of Medicine, School of Medicine, University of Miami, Miami, Fla. 33152. Peter Grendelmeier, M.D.: Formerly Arthritis Fellow, University of Miami. Miami. Fla. 331.52; present address: Langacherstrasse, Rothstein Street. 5454 Bellikon AG, Switzerland. Emilio Rodriguez, M.D.: Formerly Arthritis Fellow, University of Miami, Miami, Fla. 33152;present address:4213 North Miller Road, Scottsdale, Ariz. 85251. Requests for reprints may be addressed to: John H. Talbort. M.D., Commodore Club. I77 Ocean Lane Drive, Key Biscayne, Fla. 33149. o 1975 by Grune & Stratton. Inc.

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the hands, feet, knees, and ankles, with formation of subcutaneous tophi over the olecranon process and in the auricle of the ear. X-rays showed osseous tophi in hands and feet. The course of his disease was fulminating. An older brother had a similar age of onset and yet a third brother also had gout, but details were not given.’ Their family came from an indigenous community in South Carolina, where food was scarce and protein intake probably limited. In spite of a subsistence level diet, tophi developed, and each responded well to colchicine when the drug was administered. Since the observations were made at a time when probenecid was not available, there is no record of a therapeutic response to any antigout drug beyond colchicine. Cohen utilized an ingenious device in tracing the geneology covering four generations. He went to the family Bible where he discovered various mixtures of white, black, and Indian blood among the great-grandfathers and great-grandmothers which continued into the succeeding generations. Cohen postulated that7 “these patients may have inherited their gouty diathesis from the white race,” a statement that probably is invalid in view of the recognized world-wide distribution of gout today. I do not recall examining either a black male or a black female with gout in the outpatient department at the Massachusetts General Hospital in Boston during my earlier years of interest in gout in the 1930s and 1940s. The catchment area for clinic patients at this hospital included a majority of first or second generation immigrants from Europe. This was supplemented by a few blacks who were migrating to northern cities, but not in the large numbers that followed World War II. I encountered a very slightly modified experience during the years 1946-1959 in Buffalo, where the number of blacks had increased in relation to whites. 1 reported one black male with acute attacks of gouty arthritis, secondary to sickle cell disease, seen at the Buffalo Veterans Administration Hospital.8 My associates also showed me a black female with gout seen in the arthritis clinic at the Buffalo General Hospital.g I saw her at the time of the first attack of acute gout following melena, a contributing factor in inciting an acute attack. The patient was 47 yr old and had a long history of duodenal ulcer and bleeding, but no previous complaints of arthritis or joint disease. She continued to have her menstrual periods. The diagnosis of gout was suspected because of the site and acuteness of the arthritis, and a therapeutic trial of colchicine was given with relief of “50% of her pain.” X-ray changes of the hands and feet were present, and, in spite of rather characteristic findings of gout, the fact that she was female and presented some atypical features of gout, including changes of one ulnar styloid process typical of rheumatoid arthritis, an RA latex and an LE cell prep were ordered. These tests were negative initially and at a subsequent examination. Urinary excretion studies showed a reduced ability to excrete uric acid. The serum acid concentration ranged from 8.3 mg-13.0 mg/lOO ml. Since she was not on my service, I saw her only once, and the subsequent report does not mention administration of probenecid or colchicine prophylactically, which should have been considered in such a patient. In 1953, Pearlman and associates1o reported a case of gout in a black female, a 50-yr-old with joint pains for 7 yr. The initial episode occurred in the right great

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toe, with complete subsidence of symptoms 1 wk later. Her menopause occurred at the age of 46, 3 yr after her first attack of joint distress. Her blood pressure, which was as high as 170/l 10, was treated with mercurial diuretics. On physical examination, there were deformities of the toes and hands and cystic swelling of the olecranon processes. One olecranon mass was lemon-sized, and white cloudy fluid was recovered which contained uric acid crystals. The serum uric acid was as high as 9.3 mg/lOO ml. X-rays of the spine showed osteoarthritis, and films of the hands and feet showed deformities which were highly suggestive of rheumatoid arthritis. Notably, there was a spindle-shaped deformity of the right middle finger, cystic changes at the heads of both first metatarsals, and subluxation of the metatarsophalangeal joints of both great toes. An excellent response to probenecid 1.5 g/day was noted. A 60-yr-old black female with gouty arthritis was described by Bartfield in 1954.” The family history was negative for gout; her menstrual periods had stopped many years earlier, and she also suffered from hypertension. Her first attack of gout occurred in the right ankle and right great toe 5 yr earlier. Subcutaneous tophi yielded chalky material. X-rays of the feet showed irregular destructive erosions characteristic of gout, and hyperuricemia was present. She failed to respond to colchicine initially, but later “the relief was dramatic.” Eventually she was placed on a maintenance dose of colchicine 0.6 mg/day. Kuzell and associates reported selected aberrations on 250 patients with gout in 1955 from their clinic in San Francisco. I2 They stated that “there were no Negroes in this study,” but created the impression that rheumatoid arthritis was considered rather seriously in the differential diagnosis on several occasions. The change in belief of the rarity of gout in the blacks, and especially in black females, can be identified specifically with the report by Rodnan and Golomb of the University of Pittsburgh Clinic in 1958. I3 They assembled six cases of gout in black females and added a seventh in the addendum before publication. The ages varied from 41 to 71 yr. Four of the first six patients had subcutaneous uric acid deposits. Two were critically hypertensive, two were moderately so, and two were normotensive. The uric acid was elevated in all patients. Renal disease was evident in all but one, either by retrograde pyelography, delayed PSP excretion or elevated concentration of nonprotein nitrogen in the blood. Five of the six had proteinuria. There was no family history of gout recognized in any of the patients, but various mixtures of white, black, and American Indian appeared among their ancestors. The gouty symptoms in each of the patients appeared after the menopause, and all except one showed an excellent response to a full course of colchicine. Subcutaneous tophi were noted about the hands, while osseous tophi of hands or feet or both were evident by x-ray. One patient had arteriolar nephrosclerosis and chronic pyelonephritis, as well as secondary hyperparathyroidism. One patient who died, probably in renal failure, had a uric acid of 17.6 mg/lOO ml. Fourteen years after the onset of symptoms of acute arthritis, subcutaneous urate tophi developed, and areas of cystic erosion were seen in the bones of the hands and feet. Another patient developed acute arthritis at the age of 38 while still menstruating, and on one occasion had an excellent response to a full course of

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colchicine. Another female developed her first attack of gout at the age of 46, 1 yr after cessation of menses. Colchicine was ineffective in treating the acute arthritis. The patient mentioned in the addendum was a 60-yr-old female whose maternal grandmother was white. The serum uric acid was 9.2 mg/lOO ml. Colchicine 4.0 mg orally was followed by a prompt subsidence of fever and marked relief of joint pain. This was only her second attack of acute arthritis. Rodnan and Golomb13 accepted the fact that the demonstration of urate deposits, a combination of a family history of gout, passage of urate stones, hyperuricemia, characteristic acute arthritis, and obvious relief of symptoms with a full course of colchicine continued to serve them well in the detection of the disease in the pretophaceous stage. However, they cautioned that when colchicine is given several days after the onset of the acute gouty attack, the effects of the drug may be unimpressive. The finding of hyperuricemia does not necessarily implicate a gouty origin of acute arthritis. They placed considerable reliance upon the identification of urate crystals obtained by needle biopsy of the synovial membrane. At the present time, the identification of uric acid crysals in synovial fluid obtained by simple aspiration of an effused joint or by washing a joint space with novocaine has a higher percentage of positive results and is simpler to perform. None of the patients was considered to have gout secondary to sickle cell anemia or any other type of blood dyscrasia. The type of gout was primary or familial, even though a family history was positive in only two of the six. The ancestors of two other patients were white. An American Indian was an ancestor of one. There were three pregnancies in the group; each terminated in spontaneous abortion. The pregnancies preceded acute attacks of gouty arthritis by many years. This corresponds with the anticipated low fecundity or low incidence of living children of females, either black or white, with gout. However, Stecker, Hersch, and Solomon found fertility in females to be unaffected by hyperuricemia.14 An abnormality of renal function or structure was found in each of the patients. This included renal insufficiency, restriction of glomerular filtration and renal blood flow, an elevated blood nonprotein nitrogen or impaired function by retrograde pyelography. Examination of the kidneys postmortem in four of the patients suggested chronic pyelonephritis, and, in another, pyelonephritis with arteriolar nephrosclerosis. In 1960, Turner, Frank, van Ausdale and Bollet15 submitted a report of their experience with 74 cases of gout (of which 45 were black) seen at two large municipal hospitals in Detroit. There were 55 males and 19 females. In their series of 19 females, 14 were black, and among the 55 males, 31 were black. This was a ratio of 2.9:1 for males and 2.8 times as many black females as white females. This corresponded to the ratio of black to white patients in the hospital population. The clinical findings were not unlike those of white patients; these included podagra of the great toe, and, frequently, visible tophi. Three of the black females experienced one or more attacks of arthritis prior to the menopause, and one had

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tophi. The response to colchicine proved to be a valuable diagnostic feature in each patient who received this drug, including all 19 females who experienced a satisfactory clinical response. Rheumatoid arthritis was considered frequently in the differential diagnosis because of the polyarticular involvement. They concluded that no significant racial differences existed in the incidence of gout when data were compared to statistics for hospital admissions in the Detroit area. In 1965, Salzman, Howell and Ricca16 reported their experience from the University of Miami clinics, from which this report comes. It was impossible to determine how many blacks in this review were counted in the previous study a decade ago. Surely a few are duplicated, but a significant majority of blacks in this series have not been previously counted. Thirteen black females and 25 black males were reported in 1965. Since 50% of their series was black, while only 25% of the total hospital population was black, their data suggest that a disproportionate number of blacks suffered from gout. Our study of gout in the blacks is restricted, not comprehensive. We have merely seized the opportunity to report clinical observations in 65 cases, with a relatively high ratio of females, in this contribution to the gout literature. The cases were gathered as the patients attended the arthritis clinics at the Miami Veterans Administration Hospital or the Jackson Memorial Hospital, Miami, Fla. No attempt was made to retrieve any black patients with gout from the records, nor were announcements sent out to the medical community noting any special interest in blacks with gout. In substance, little more information is included than a few vital statistics. Any positive or negative data on family history of gout is meaningless, since many of the patients had little recollection of their parents, not to mention diseases. Several of the patients were not even aware of the name of one of their parents, especially the fathers, because of the inherent high desertion rate in this ethnic group. Emphasis was placed on age of onset of acute arthritis, conception after onset of arthritis, continuation of menstrual cycles, or menopause, and black, white, or American Indian ancestors. Such data are relatively reliable, especially when positive. The diagnosis of gout was usually based on identification of urate crystals in the synovial fluid or a subcutaneous tophus. The frequency and sites of acute attacks of arthritis, the presence or absence of tophi, and the therapeutic response to a full course of colchicine for the acute arthritis were noted. Often the clinical response to probenecid or allopurinol could not be adequately determined. This was recorded only when a positive statement was incorporated in the record. The black race may have several factors that put them at greater risk for the development of gout than whites. Hypertension, unrelated to gout, traditionally is thought to be more frequent in blacks than whites. Hypertension is a common ancillary feature of gout, probably in all ethnic groups. The use of thiazides and other diuretic agents in the hypertension regimen is widespread. Since thiazides alter the transport of uric acid by the kidney, thus depressing the excretion of uric acid, such diuretics may be the inciting factor in producing gouty arthritis in an otherwise nongouty person, black or white, male or female. Several instances of thiazide-associated gouty arthritis appeared in our series. Whether the thiazides

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acted as a trigger mechanism, or caused gouty arthritis de noveau in a nonsusceptible person is uncertain. It is our belief that most examples of iatrogenic thiazide gout fall in the de noveau category. If gouty arthritis develops in a patient receiving a thiazide diuretic for the treatment of cardiac failure, hypertension, or other disturbances, our experience with the addition of prophylactic antigout drugs is thoroughly satisfactory. Neither class of drugs nullifies or augments the potency of the other. Colchicine, probenecid, and allopurinol may be continued with equally satisfactory results as in the patient with primary gout. The incidence of tuberculosis in blacks is higher than in whites, and pyrazinamide, a drug used at one time in the treatment of tuberculosis, may cause hyperuricemia and, subsequently, gouty arthritis.17 In some patients with sarcoidosis, arthralgia or an acute arthritis similar to gouty arthritis has been observed. The beneficial response of sarcoid arthritis to colchicine has caused some confusion regarding the use of this drug as a diagnostic tool in gout. Since the incidence of sarcoidosis is appreciably higher in blacks, the probability of sarcoid arthritis must be considered. Again, none of our blacks with gout was treated with pyrazinamide or had a secondary diagnosis of sarcoidosis. The association of sickled red blood cells or hemoglobin S or C replacing hemoglobin A with the development of acute attacks of arthritis simulating gouty arthritis is well documented.8 The persistent elevation of serum uric acid is thought to be associated with an increased turnover of nucleoproteins, similar to that obtained in several other blood dyscrasias,18 and may lead to gouty arthritis. Sickle cell anemia may also be associated with aseptic necrosis and septic arthritis. Vascular thrombosis may lead to bone infarction, periosteal elevation, and a serous or hemorrhagic synovial effusion.‘g The features of gouty arthritis in a black with sickle cell disease are the same as gout unrelated to sickle cell disease. The sudden onset of acute arthritis in a peripheral joint, especially the great toe, knees or hands, with identification of urate crystals in the joint and an elevated serum urate, are convincing. Thus Pate120observed a serum uric acid of 13.8 mg/ 100 ml in a black with sickle cell disease and acute arthritis, and, although crystals were not found in the synovial fluid, the diagnosis of gout was established at synovectomy. No mention was made of response to colchicine. None of our patients had sickle cell anemia, while three showed the sickle cell trait. The relationship of uric acid level to certain risk factors, notably hypertension and coronary heart disease among blacks, has been studied by Klein, Coroni, and associates.*1 They found no significant difference in serum uric acid levels between blacks and whites. In a study of 2530 persons in Evans County, Ga., the mean serum urate levels for black and white females was 4.8 and 4.9 mg/ 100 ml, respectively. The higher serum urate level in males than in females of approximately 0.5 mg/lOO ml agrees with earlier observations. The study by Klein et al. of those with an elevated uric acid showed that the prevalence of hypertension (160/90 Hg/mm or greater) was higher in hyperuricemics, and the increased prevalence of coronary heart disease in hyperuricemics was secondary to increased body size. These studies do not provide definite conclusions, positive or negative, regarding the incidence of gout in blacks versus whites.

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The patients described in this review have been followed in the University of Miami out-patient arthritis, medical, and other clinics, and, on occasion, have been hospitalized on the general medical teaching wards of our center.22 This has posed certain problems worthy of comment. Patients attending these facilities are cared for by medical students, house officers, or faculty members. In the course of time, the patient may be attended by many different physicians, sometimes without the benefit of old records. Each doctor and trainee is encouraged to act independently, or when requested, with guidance, in deriving their diagnostic and therapeutic conclusions. These facts may account, in part, for some of the divergent diagnoses and various treatments employed in the management of the patients described below. CASE MATERIAL

Several short case histories are presented which illustrate one or more aspects of gouty arthritis in blacks, usually complemented with one or more roentgenograms of the joints or neighboring structures. The first case is the only female in the series who bore a living child after the onset of gout. G. R. a 4%yr-old black obese female with Indian ancestry on both sides, had her first attack of acute gouty arthritis at the age of 34. She was extremely fertile and during her menstrual years was pregnant 12 times; several of the infants died, but five children are living and well. She was last pregnant at the age of 38, four yr after her first attack of gout. A son, now 11 and well, was the product of her last delivery. She suffered from hypertension, but never received diuretics or other hyperuricemic drugs. On physical examination, she showed no evidence of tophi at any time. The findings during an acute attack were clinically characteristic. She responded well to a full course of colchicine and, although prophylactic medication-l.5 mg colchicine and 300 mg allopurinol-were recommended daily, the intake was sporadic; when she omitted the drugs for a time, symptoms frequently recurred. Her blood pressure was as high as 170/100, but thiazide diuretics were never given. Serum uric acid levels off antigout drugs were as high as 14 mg/lOO ml, and, while she was on prophylactic medication, fell not lower than IO mg/lOO ml. Uric acid crystals were identified from joint fluid on two occasions.

The next black female suffered from tophaceous gout for almost 20 yr. Additional features of her case include: calcification of the internal meniscus of the knee (compatible with chondrocalcinosis), but no manifestations of diabetes mellitus or hemochromatosis, a slight increase in fetal hemoglobulin with a negative sickle cell preparation, a diagnosis of rheumatoid arthritis made by general medical interns on several occasions, and an unexplained secondary anemia. In spite of these aberrations, the clinical diagnosis of familial gout was amply justified. M. A., a 60-yr-old black female whose mother was Indian, was first seen in 1971 for a retinal detachment of the left eye. An exploratory laparotomy for a tubo-ovarian abscess, with removal of the uterus, tubes, and ovaries was performed at a later time. A barium enema showed extensive diverticulosis. She gave a history of acute intermittent gouty arthritis beginning in 1956, involving hands, elbows, knees, and feet, with tophi. Because of extensive tophaceous gout, her medication included colchicine, I .5 mg, probenecid 1.5 g, and allopurinol 300 mg/daily. A satisfactory response to colchicine for acute symptoms was recorded. Urate crystals were identified from tophi and joint fluid, but no calcium pyrophosphate crystals were seen. The hematology consultant could not progress beyond a diagnosis of idiopathic secondary anemia. In 1970, serum uric acid concentrations exceeded I2 mg/ 100 ml with a BUN of 20 mg/lOO ml. RA factor, ANA, and sickle cell preparations were negative. Hemoglobin electrophoresis showed fetal hemoglobin of I .3%.

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Fig. 1. AP view of left knee of M.A. with calcification of the cartilage of the lateral compartment, small erosions of the medial border of the proximal tibia beneath the medial plateau, and minor degenerative changes (See Figs. 2.3. and 41.

In 1971, her blood pressure was 190/l 10, and a thiazide diuretic was added to her regimen, which did not seem to aggravate the clinical course of her gout. At other times, her acute attacks responded to phenylbutazone. In July, 1972, the hemoglobin was 11.4 g/100 ml and hematocrit 36%. Having bad considerable trouble with her shoulder, an x-ray of November 21, 1972 showed early arthritic changes in the right shoulder, with questionable calcification of cartilage. A statement by an emergency room physician stated that this patient had been “followed for rheumatoid arthritis for several years.” Such a statement was hardly justified upon critical review of record and patient. X-ray of the knee (Fig. I) showed calcification of the meniscus, while the lateral projection (Fig. 2) showed bony erosions of the tibia1 tubercle. An x-ray of the left hand showed minor changes suggestive of rheumatoid arthritis (Fig. 3), and the right hand showed boutonniere deformities (Fig. 4). a feature most frequently seen in rheumatoid arthritis. X-rays of the feet were characteristic of gouty arthritis.

Lateral of left knee of M.A. showing Fig. 2 the bony erosions of the tibia1 tubercle (See Figs. 1.3,and 4).

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Fig. 3. AP left hand of M.A. with juxta-artitular osteopenia, soft tissue swelling about the second, third. and fourth proximal phalangeal joints and narrowing of multiple proximal phalangeal joint spaces (See Figs. 1,2. and 41.

The next patient had been diagnosed as having rheumatoid arthritis on the basis of a 20-yr history of polyarthritis. This diagnosis had been made despite repeatedly (3 X) negative RA tests. Recently, she was placed on thiazides for hypertension, and later uric acid crystals were identified in the joint fluid. She responded well to a full course of colchicine, remained symptom-free while on a full antigout regimen (colchicine, probenecid, and allopurinol daily), but her

Fig. 4. Oblique view of right hand of M.A. with boutonniere deformities of the second. third, fourth. and fifth digits, highly suggesti ve of rheumatoid arthritis (See Figs. 1,2. and 3).

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Fig. 5. Oblique view of left foot of L.B. showing cystic lesions of the first through fourth metatarsal heads, hypertrophic changes of the first metatarsophalangeal end interphalangeal joints, and deformity of the fifth metatarsophalengeal head.

symptoms promptly returned when she omitted the drugs. The best diagnosis seems atypical rheumatoid arthritis for 15 yr, plus gout secondary to thiazide ingestion the past 5 yr. X-rays of the right foot (Fig. 5) show typical lesions of gouty arthritis. The patient developed some evidence of liver disease while on allopurinol; this subsided when this drug was discontinued. There was no evidence in the record that she had been given probenecid when allopurinol was discontinued. I. B., a 75-yr-old black female with an Indian grandfather, was first seen in 1963, with a pelvic mass which was removed surgically. The postoperative diagnoses were fibroma, chronic pelvic inflammatory disease, and pyelonephritis. Her arthritis began in 1954, at the age of 55. It involved the right arm, hands, fingers, shoulder, ankles and both knees, which were swollen and tender. A diagnosis of rheumatoid arthritis was made from clinical and x-ray findings, despite a negative RA latex. The sickle cell preparation was negative. The patient was next seen in the hypertensive clinic in 1965, with a blood pressure of 200/95. The eye grounds showed grade II vascular changes. A year later, a diagnosis of degenerative joint disease was made. In 1967, she was placed on thiazides for her hypertension; it was probably the drug responsible for her gouty arthritis. The diagnosis of gout was first made in November 1969. Uric acid crystals were identified in a synovial fluid specimen obtained from the left ankle. She was treated with colchicine 1.0 mg and allopurinol 300 mg a day, but the latter drug was discontinued when liver disease developed. lndomethacin was also given at times. When, on occasion, daily colchicine was stopped, acute gouty arthritis developed. Uric acid crystals were seen a second time in a knee joint effusion. She admitted that she was well protected when she took colchicine (1.0

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mg) daily, and poorly controlled when she went off the drug. Her blood pressure remained about 156/ 70 on antihypertensive medication. When the patient was seen in clinic in 1971, the BUN was 10 mg/lOO ml, and serum uric acid ranged from 6.7 mg to 8.0 mg/lOO ml. Urine protein was normal and hemoglobin 12.5 g/100 ml. An alkaline phosphate of 200 units, an SGOT of 130 units, and an abnormal liver scan were all consistent with cirrhosis. X-rays of both feet taken in 1972 showed erosions at the base of the metatarsal beads and a gouty tophus on the great toe. When she was last seen in January 1974, her blood pressure was 140/80, she was taking hydrochlorothiazide and colchicine, 0.5 mg/daily, and doing well.

The next patient was a male who was known to have gouty arthritis for 10 yr, sickle cell trait for 5 yr, chronic pyelonephritis for an indefinite period, and, more recently, an endocrine syndrome which could not be diagnosed definitely. His joint symptoms responded well to antigout drugs, and his muscle weakness responded to a high potassium intake. If this represents gouty arthritis secondary to a sickle cell trait, it was the only manifestation of a hemoglobinopathy. A. C., a 63-yr-old black male, a gardener by occupation, presented atypically with acute arthritis of the right knee. Other medical problems included chronic pyelonephritis associated with stricture of the urethra which required dilation under anesthesia, and a sickle cell trait which was detected several years after the initial attack of gouty arthritis. Blood studies showed a hemoglobin of 9.1 g/l00 ml; fetal hemoglobin was 31.2% by electrophoresis. He had received a number of blood transfusions for the anemia. Serum uric acid was 9.4 mg/ 100 ml and BUN ranged from 23 mg to 65 mg/lOO ml. After extensive studies, a syndrome of muscle weakness, with hypoaldosteronism, hypokalemia, and hypochloremic acidosis was discovered. The patient was placed on a high sodium diet to keep his potassium normal, and he was given fludrocortisone acetate, which kept his potassium as high as 7. I mEq/liter. His prophylactic antigout medication included colchicine, 1.0 mg, allopurinol 300 mg, and indomethacin 75 mg a day. X-rays of the feet (Fig. 6) showed changes of gouty arthritis with multiple cystic lesions of the first and fifth metatarsophalangeal joints.

Another female gave a history suggestive of rheumatoid arthritis. She had a mild anemia, but a negative sickle cell preparation, no fetal hemoglobin and a negative RA factor. Tophi about the joints were readily apparent. Urate crystals were identified from tophi as well as synovial fluid. A. G., a 76-yr-old black female, was seen in 1961 in the hospital with an acute right knee of 3 wk duration, preceded by a similar episode in the left knee. The clinical diagnoses included gouty, degenerative, and rheumatoid arthritis. The patient had a 6-yr history of arthritis of both legs, ankles,

Fig.

6.

AP

showing

A.C. the

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left

fifth

joints.

and

view cystic left

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feet

lesions first

metatarsophalangeal

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Fig. 7. AP view of left hand of A.G. showing tophaceous changes in the metacarpophalangeal and proximal interphalangeal joints, swelling of the third proximal interphalangeal joint. and a flexion deformity of the second proximal interphalangeal joint; some of the changes seen in rheumatoid arthritis.

fingers, and the right shoulder. A hypochromic microcytic anemia with a hemoglobin of 9.5 g/l00 ml, and a reticulocyte count of 2.5% was found, for which she was given iron. Hemoglobin electrophoresis was normal and the RA factor was negative. Although a trial with colchicine was recommended, this was not done initially. Later, a favorable response to colchicine was obtained. She was placed on colchicine, 0.5 mg, and probenecid 1.0 g daily, and had three attacks of gout in the following 2 yr. She responded well to a full course of colchicine at those times. Her blood pressure was 140/84. Several tophi were present about the hands and elbows; aspiration of the knee showed urate crystals in the synovial effusion. Bone marrow examination, because of persistent anemia, was unremarkable. Colchicine was assumed to he responsible for the anemia by a hematology consultant, although the anemia was present prior to colchicine administration. The patient was hospitalized in 1965 for a fracture of the femoral neck, which was treated with closed reduction and pinning. She developed decubital ulcers and received surgical treatment for this complication. She was taking probenecid I g a day for about 3 yr. Subsequently, allopurinol was sub stituted for probenecid, and a presumptive diagnosis of rheumatoid and degenerative arthritis (Fig. 7). as well as tophaceous gout was made. Uric acid crystals again were recovered from a joint. It is impossible to determine whether there was any difference in response between colchicine and prolnmecid or colchicine and allopurinol, since a good response followed the regular use of either combination. The patient suffered no more than one attack of acute gouty arthritis per year. The last serum uric acid was 8.4 mg/lOO ml, serum creatinine 1.8 mg/lOO ml, and there were 5 mg/lOO ml protein in the urine. Mild hypertension was first noted in 1970, and cataracts developed in 1971. When last seen at age 75, she was doing well on allopurinol, 300 mg, and colchicine, I .5 mg, a day.

The next patient complained of intermittent distress in multiple joints since the age of 36. He had severe hypertension, and in spite of medication suffered a CVA with a right-sided hemiplegia. Medication included thiazides given long after the arthritis symptoms first appeared. Since the diagnosis clearly was tophaceous gout, the cause probably was primary gout, aggravated by thiazides. The clinical problems of hypertension and stroke overshadowed the arthritic complaints, and he was seen by the arthritis division at infrequent intervals.

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Fig. 8. Lateral view of right foot of T.H. showing cystic lesions bones attributed either to a severe stroke or gout (See Fig. 9).

of the navicular

and cuneiform

T. H., a 58-yr-old black male, was admitted to the hospital for the first time in 1967 for an acute cerebrovascular accident associated with dizziness, weakness of the right side, slurred speech, and semicoma. Review of his past history showed that hypertension had been present for more than 20 yr, and that he probably had suffered his first attack of acute arthritis at the age of 36, but no specific diagnosis was made. He was given various antihypertensive medications, including thiazides eventually. Blood pressure was as high as 220/150. The right hemiplegia was apparent, as were other neurologic signs associated with a recent stroke. Laboratory studies showed 100 mg/lOO ml proteinuria, hemoglobin 16.9 g/100 ml, serum uric acid 10.4 mg/lOO ml, BUN 28 mg/lOO ml, and serum creatinine 1.8 mg/ 100 ml. After a diagnosis of brain stem infarction was made, the patient was sent to a rehabilitation center and followed in the neurologic and hypertensive clinics. He was not seen in the arthritis clinic until 1972, when he complained of severe pain in the left elbow, knee, and ankle, and showed a large soft tissue swelling, with a discharging sinus on the lateral aspect of the right foot. Uric acid crystals were recovered from the discharge. The serum uric acid was 12.0 mg/lOO ml, and a diagnosis of gout was made. This well-developed case of tophaceous gout may have been aggravated by the thiazides, but the arthritic symptoms preceded the antihypertensive medication by many years. The x-rays of the right foot (Fig. 8) showed osteoporosis attributed to disuse following the CVA, and multiple subcortical erosions without evidence of osteomyelitis. X-ray of the left foot (Fig. 9) showed cystic lesions in the tarsal bones typical of gout.

The next patient had a number of medical problems, including acute gouty arthritis following a thiazide regimen. Cystic lesions were evident by x-ray in the hand (Fig. lo), serum uric acid was as high as 11.0 mg/lOO ml, uric acid crystals were recovered from synovial fluid, and the response to antigout drugs was excellent. In spite of the long history of hypertension and gout, there was no evidence of kidney dysfunction. J. J., a 57-yr-old black male, suffered from asthma 30 yr ago, intermittent precordial pain not relieved by nitroglycerin, and a stroke, in 1956, associated with mild hypertension. Treatment of his hypertension, however, which included thiazides, was not begun until 1966, I yr before his first attack of gouty arthritis. There was unexplained clubbing of all fingers. Uric acid crystals were recovered from the synovial fluid removed from an ankle. Blood pressures as high as 192/130 were recorded. The highest BUN was 18 mg/lOO ml. Skin grafts of the left anterior foot for chronic ulceration associated with gouty tophus were carried out in 1970. In 1967, colchicine, 2.0 mg per day and allopurinol 300 mg/day, as well as reserpine and chlorothiazide, were given. A good response to antigout drugs was noted. The patient was last seen in August 1973, when he had exhausted his supply of colchicine and had a return of acute symptoms 36 hr later. Symptoms responded promptly to a full course of colchicine.

TALBOTT

ET AL.

Fig. 9. AP view of the left foot : of 1‘.H. sLhowing cystic lesions of the navicular and first and second cuneiform bones (See Fig. 8).

The next case with polyarthritis of many years duration is another example of a patient whose clinical findings suggested rheumatoid arthritis, but who eventually developed tophi from which uric acid crystals were recovered. The serum uric acid was elevated. Low back pain prompted an x-ray of the lumbar spine which showed changes consistent with a gouty tophus. L. L., a 63-yr-old black female, was first seen in the clinic at the age of 50 with a 4-yr history of polyarthritis, with relapses and remissions involving wrists, hands, elbows, knees, and ankles, with increasing limitation of motion and inability to walk without crutches. During the hospital admission mild diabetes mellitus, hypertension, albuminuria, modest elevation of BUN and serum uric acids that ranged from 8 to 12 mg/lOO ml were found. The RA latex was negative at three examinations. Xrays of the hands showed diffuse soft tissue and bony changes which in selected areas suggested either gouty, rheumatoid, or degenerative arthritis (Fig. 1 I). X-rays of the knees showed cystic lesions of gout (Fig. 12), and changes of the feet suggestive of rheumatoid or gouty arthritis (Fig. 13). A biopsy of an olecranon bursa showed urate crystals. In spite of the clinical finding of rheumatoid arthritis, the confirmed diagnosis of gouty arthritis was accepted. Five yr later, the patient was admitted to the hospital for continuing backache and some distress in the left knee. She had responded reasonably well to medication taken regularly for hypertension and diabetes mellitus, and antigout drugs taken less regularly for her gouty arthritis. A tomogram of the lumbar spine showed a punched out area (Fig. 14) which was highly suggestive of a gouty tophus. As the antigout drugs (colchicine, 1.0 mg, and allopurinol, 300 mg, daily) were taken with greater regularity, she responded well, and her back and peripheral joint symptoms were less bothersome.

GOUTY ARTHRITIS

IN BLACK

RACE

223

Fig. 10. Oblique view of left hand of J.J. showing cystic lesions of the first metacarpal head, soft tissue swelling of the fifth proximal interphalangeal joint. and multiple small osseous erosions.

Fig. 11. AP view of right hand of L.L. showing narrowing of the radio- and ulnar-carpal, intercarpal and carpometacarpal joint spaces, cystic lesions of multiple carpal bones, and the fourth and fifth proximal metacarpals, bony irregularity of the radial aspect of the proximal end of the second phalanx. The third metacarpophalangeal joint is sclerotic. eroded, and narrowed. Sywaters hooks are seen on the third and fifth metacarpal heads, soft tissue swelling and bony enlargement of the second and fourth proximal interphalangeal joints, with sclerosis, erosions, and joint space narrowing and Heberden’s nodes of the second and fourth distal interphalangeal joints (See Figs. 12, 13, 141.

224

TALBOTT ET AL.

Fig. 12. Lateral view of right knee of L.L. showing sclerosis and osseous cysts of each of the four bones making up the knee joint (See Figs. 11.13,14).

Fig. 13. Oblique view of right foot of L.L. showing sclerosis, bone cysts of distal tibia. tarsal% and first interphalangeal joint, and generalized demineralizetion. The first and fourth matetarsophalangeal joints are partially destroyed with narrowing of the joint spaces and irregularity of the joint margins (See Figs. 11,12, and 14).

GOUTY ARTHRITIS

IN BLACK RACE

225

Fig. 14. Lateral view of pelvis of L.L. A large urate tophus is seen in the disc space and surrounding area between L5 and Sl .

Another male patient was treated for gouty arthritis and rheumatoid arthritis at various times, while an x-ray diagnosis of osteoarthritis was made by the radiologist. Uric acid crystals were identified from an acutely swollen olecranon bursa and wrist. J. L. was seen first in 1970, when he complained of acute distress in the left great toe (Fig. 15) and ankle. In the past, he admitted to having morning stiffness and disseminated joint disease which included the feet, knees, and elbows, suggesting a diagnosis of rheumatoid arthritis to the medical service. Other illnesses included hypertension and alcoholism. The blood pressure was as high as 200/ 100 mm Hg. Uric acid crystals were identified in synovial fluid from the knee. The serum uric acid was as high as 10.4 mg/lOO ml. The ANA and RA latex tests were negative. Later, uric acid crystals were identified in fluid taken from an acute olecranon bursitis, and from a hot, swollen tender wrist. After his symptoms had subsided with a full course of colchicine, he was placed on colchicine, 1.0 mg, and allopurinol, 300 mg, daily, and, as long as these drugs were taken regularly, his gout remained under control. However, when his pills were exhausted, he usually developed an acute attack of gout within a fortnight, and he then returned to the clinic wearing a slipper on the affected foot.

The next patient is the oldest female in our series. She had received thiazide drugs for several years before the onset of acute gouty arthritis, which was

Fig. 15. Oblique metatarsophalangeal

view of left foot of J.L. with several small cystic lesions of the first and fifth joints.

226

TALBOll

ET AL.

Fig. 16. N. McD. an 83-yr-old black female with gouty arthritis which developed following thiazides (See Figs. 17, 18).

superimposed on osteoarthritis. Uric acid crystals were recovered several times from knee effusions. She had a relatively satisfactory response to antigout medication, while continuing the hypertensive regimen, which included thiazides. N. Mc.D., an 83-yr-old black female (Fig. 16) whose grandmother was Indian, was first seen at the age of 74 in 1965 in the medical clinic for back pain of many years duration, associated frequently with morning stiffness. She also complained of pain in her knees, ankles, and wrists. Her past history included esophagitis in 1929, pellagra, and pyelonephritis in 1947, and upper gastrointestinal bleeding in 1970. X-rays showed degenerative changes of both knees and spine, as well as cystic changes in her tarsus (Fig. 17). The VDRL was positive. Because of dizzy spells and a blood pressure of 165/80 at the age of 74, she was placed on chlorothiazide and later hydrochlorothiazide with good control of her blood pressure. A uric acid greater than 12 mg/lOO ml was recorded on a biochemical profile. On medication consisting of colchicine, 1.0 mg, and allopurinol, 300 mg/a day, the value fell to 5.3 mg/ 100 ml with fair symptomatic response. Repeated bilateral effusions of the knees showed uric acid crystals. Her complaints concerned her knees (Fig. 18) which frequently forced her to be wheelchair bound.

Fig. 17. AP right foot of N. McD. with multiple cystic lesions of the bones (See Figs. 16 and 18).

GOUTY ARTHRITIS

IN BLACK RACE

Fig. 18. AP right knee of N.McD. with prominent lateral spurs, joint space narrowing and a cystic lesion in the medial condyle of the tibia (See Figs. 16 and 17).

Another male patient suffered from multiple joint symptoms for more than 25 yr and urate tophi deposits for more than 15 yr. He responded well to colchicine and probenecid; allopurinol was added later. He had a marked elevation of blood pressure and responded well to antihypertensive medication, which included thiazides. One acute attack of gout followed 1.2 million units of penicillin. R. P., a ‘II-yr-old

black, had been well until 1959, except for one episode of acute arthritis

of the

right knee 25 yr earlier. Following an injury in 1957, he had persistent pain in his shoulders, back, and neck, as well as heat and tenderness in both knees, ankles, hips, and, to a lesser extent, in his fingers and toes. Several times he had been awakened at night by joint pains which were relieved by Empirin. He was told that he had high blood pressure, and admitted to nocturia and frequency. On physical examination,

blood pressure was 200/98.

Several tophi on the hands and ears were

evident. Both knees and ankles were warm and swollen. A diagnosis of tophaceous gout with renal involvement was made on admission, but it was noted that rheumatoid patient was given a course of colchicine 4.0 mg total, with dramatic was 9.3 mg/lOO

ml, and the RA

factor

Three

beginning penicillin,

with colchicine,

He was admitted syndrome.

urogram

he had an exacerbation

arthritis

which was

relief of pain. There

was no

symptoms during the next 7 yr.

next for acute pyelonephritis. showed poor excretion.

Urine culture showed gram-negative

The ECG was compatible

Other diagnoses on the chart included osteoarthritis

each elbow showed an olecranon geal involvement,

He was

Two weeks later, while

of acute gouty

0.5 mg, three times a day, with satisfactory

significant progression ofjoint excretory

1.0 g/a day, prophylactically.

he received penicillin 1.2 million units daily for several days for a positive serology.

days after

treated

was to be ruled out. The

was positive at 1:640. The urine showed albumin.

placed on colchicine, 0.5 mg, and probenecid, still hospitalized,

arthritis

relief of pain. The serum uric acid

tophus (Fig. 19). X-rays

soft tissue swelling with subluxation

organisms.

An

with a Wolf-Parkinson-White

and rheumatoid

arthritis.

of the hands showed proximal

of the first metacarpophalangeal

X-rays

of

interphalanjoint on the

right, with increased bony sclerosis. The patient was next admitted and an olecranon

ml, and, even though he appeared and probenecid,

in February

tophus discharging

1962 with acute arthritis

of the feet, tophi in both ears,

urate sludge. The serum uric acid was as high as 12.4 mg/lOO

to be on adequate prophylactic

medication

of colchicine,

1.5 mg,

1.0 g daily, he developed an acute effusion of the right knee, and swelling and pain of

the right elbow and wrist. He was started on phenylbutazone,

100 mg every 6 hr. and colchicine, 0.6

228

TALEOTT ET AL.

Fig. 19. Lateral of left elbow of R.P. with soft tissue swelling of the olecranon bursa and erosions of the olecranon process at the insertion of the triceps tendon (See Figs. 20 and 21). mg twice daily, with only moderate relief. At the time of discharge, he felt better than he had for several months. Diabetes mellitus was discovered in 1963, and he was placed on regular insulin. He had one episode of myocardial failure. The next admission was for a gunshot wound in 1966. He remained on colchicine 1.5 mg and probenecid I.0 g a day, and allopurinol 200 mg/day was added. X-ray showed a renal calculus, a calcific density overlying the lower pole of the left kidney. The SMA uric acid was greater than 12 mg/lOO ml, BUN 26 mg/lOO ml. A t ransurethral prostatectomy was performed; the pathologic diag-

Fig. 20. Oblique left foot of R.P. with joint space narrowing and cystic lesions of the first metacarpophalangeal joint suggestive of gout. Subluxation, hypertrophic changes of the first. and cock-up toe deformities of the second, third. fourth and fifth digits were suggestive of rheumatoid arthritis (See Fig. 211.

GOUTY ARTHRITIS

IN SLACK RACE

229

nosis was adenocarcinoma. In 1967, he had a mild stroke from which he made a satisfactory recovery. At that time, probenecid was withdrawn because “no significant effect could be recorded.” At the next admission on 2/23/71, no evidence of metastatic bone lesions was seen; the bone scan was negative and the acid phosphatase was 3.2 mg/lOO ml. A recent follow-up reported a satisfactory response to prophylactic antigout medication. Uric acid SMA varied between 7.2 and 8.7 mg/lOO ml, and BUN as low as 10 mg/lOO ml. Current medication includes methyldopa, a thiazide diuretic, allopurinol, and colchicine daily. His gout remains quiescent, and his blood pressure is controlled as long as he takes his medicine. X-rays of the left foot (Fig. 20) show cystic lesions typical of gout and deformities of the toes typical of rheumatoid arthritis. Osseous lesions of the knee (Fig. 21) are typical of gout.

Another patient had joint pain for more than 15 yr, subcutaneous tophi, some symptoms suggestive of rheumatoid arthritis, and x-ray evidence of crippling changes of this disease (Fig. 22, 23). The RA latex was negative. He developed a lichen planuslike dermatitis, probably from allopurinol, which eventually was controlled with increasingly larger amounts of the drug and antihistaminics. He responded well to prophylactic antigout medication. A. T., a 60-yr-old black male, was first seen in the clinic in 1965 with a history of intermittent attacks of acute arthritis for several years, and a diagnosis of “gouty nephropathy.” Intermittent albuminuria had been present for a number of years. He had been on 1.0 mg colchicine and 2.0 g probenecid a day for more than a year with satisfactory control of symptoms. It was only when he stopped the drugs that acute symptoms returned. Later, probenecid was replaced by allopurinol 100 mg three times a day. Past history included a positive VDRL and gonorrhea without arthritis in 1954. The patient was hospitalized in 1969 for generalized lichen planus, or a lichen planuslike drug reaction, which was thought to be related to allopurinol which was started 2 yr earlier. At the time, there were large tophi on the elbows and smaller ones on the ankles. In spite of the drug reaction, and because of the diagnosis of gouty arthritis and significant renal disease, he was desensitized to allopurinol with increasingly larger doses plus antihistaminics. Allopurinol 100 mg plus probenecid

Fig. 21. AP right knee of R.P. with loss of joiint space. osseous erosions of the lateral femoral epicondyle and lateral Itibia1 condyl le (See Fig. 20).

230

TALBOTT

ET AL.

Fig. 22. Lateral of both hands of A.T. with boutonniere deformities of the right fourth and left third digits and cystic lesions of the right distal radius, multiple carpal bones, and fourth metacarpal head (See Figs. 23 through 31).

1.0 g a day which was added later, were well tolerated. The BUN was as high as 67 mg/lOO ml; creatinine, 2.7 mg/lOO ml; and serum uric acid ranged from 9.8 mg to 13.6 mg/lOO ml. The hemoglobin concentration was 10.6 g/100 ml, and the RA latex was negative. An enlarged olecranon bursa on the left yielded urate crystals. The blood pressure was 130/80 mm Hg. X-rays on admission (Figs. 24 and 25) showed osteolytic lesions of the first metatarsal and the

Fig. 23. Hands of A.T. with changes frequently seen in advanced rheumatoid arthritis (See Figs. 22 and 24 through 311.

GOUTY ARTHRITIS

IN BLACK

RACE

231

Fig. 24. AP of right foot of A.T. with cystic changas of the first matatarsophalangel joint. hallux valgus, and cystic lasions second through fifth of the matatarsophalangeal joints (See Figs. 22,23, and 25 through 31). portion of the proximal phalanx of both great toes. Soft tissue swelling was evident about the metacarpophalangeal joints. Over the lateral malleolus of the right foot was a soft tissue swelling (tophus) overlying an osseous lesion (Fig. 26). Later, destructive changes were seen in the inferior of the patella (Fig. 27) which were interpreted as either a gouty tophus or osteoarthritis. Hypertrophic and then degenerative changes of the spine were noted. Over the right elbow (Fig. 28) was a large tophus which was also evident by x-ray (Fig. 29) that yielded urate crystals. Figures 30 and 31 are pelvic x-rays taken 6 yr apart that show progressive cystic lesions of the sacroiliac joints. The acute attacks of gout occured mainly in the patient’s hands. He was free of acute arthritis for as long as 6 mos while on the three-drug combination daily. Symptom-free periods then stretched into I yr. Tophi began to regress, and the lowest serum uric acid was 4.1 mg/lOO, with a BUN of 31 mg/ 100 ml. Occasionally, he would develop an effusion in the right knee which was not particularly painful and was thought to be associated with osteoarthritis. The several diseases did not appear to affect adversely the value of the antigout drugs, nor did they appear to hasten the chronic tophaceous changes. proximal

The next patient suffered her initial attack of acute gout on the third day following surgery. Several years later, she was found to have mild hypertension

232

TALEOTT

ET AL.

Fig. 25. AP left foot of A.T. with mild hiallux valgus deformity, multiple cystic lesions of’ the first and fifth metatarsophalangeal joints, two small cysts of the first interphalangeal joint, and juxta-articular osteopenia of the second thrc,ugh fifth metatarso-phalangeal joints (See Figs 22 through 24 and 26 through 31).

and albuminuria, and was placed on antihypertensive drugs, including thiazides. Her response to antigout therapy continued to be satisfactory. The sickle cell preparation was positive, and small amounts of hemoglobin C were found in her blood. The hypertension is believed to be associated with the gout, but the gout was not related to the abnormal hemoglobin. D. S., a 62-yr-old black female, suffered an acute attack of arthritis of the left foot and knee at the age of 50, 3 days following surgical removal of an adrenal cyst. The diagnosis of gout was entertained, and she responded well to a full course of colchicine. It was not until several years later, however, when she had an increasing number of acute attacks, that she was placed on prophylactic colchicine, 1.0 mg, and allopurinol, 300 mg/daily. She responded well to this regimen. At this time her blood pressure was found to be elevated (190/ 130), and she was placed on antihypertensive therapy which included thiazides. She was followed in the hypertensive and arthritis clinics. The BUN was 26 mg/lOO ml, the urine showed 100 mg of albumin, and serum uric acids were as high as 14 mg/lOO ml. The hemoglobin was 12 g/100 ml; a sickle-cell preparation was positive; small amounts of hemoglobim C were identified in the blood. Her gout remained under control even though she used antihypertensive medication as long as she took her antigout drugs.

GOUTY ARTHRITIS

Fig. 26. and

lateral

27 through

Right

IN BLACK

foot of A.T. with tophi

malleolus

(See

Figs.

233

RACE

of great toe

22 through

25

and

31).

Fig.

27.

Lateral

vith an erosive latella.

soft

alcification 12 through

lesion

tissue

view

of

right

knee

of the inferior swelling

of the quadriceps 26 and 28 through

of

the

tendon 31).

of

aspect knee (See

A.T.

of the and Figs.

234

Fig. 28. Lateral right elbow of A.T. with large olecranon tophus with some demineralization of bone but no cystic lesions (See Figs. 22 through 27 and 29 through 31).

TALEOTT

Fig. 29. Lateral soft tissue swelling demineralization of Figs. 22 through 28

ET AL.

of right elbow of A.T. with of the olacranon bursa and the olacrenon process (See and 30,311.

GOUTY ARTHRITIS

IN BLACK RACE

235

Fig. 31. AP of pelvis of A.T.; 6 yr after Fig. 30 with progression of gouty changes in right sacroiliac joint and well developed cystic changes in left (See Figs. 21 through 29).

In 1968, there were minimal x-ray changes of the right hand, including tive of gout. X-rays of the knees showed degenerative changes bilaterally, joint spaces.

punched-out lesions suggeswith some narrowing of the

The oldest patient in this series, a black male, had suffered from gouty arthritis for more than 40 yr. He also had pulmonary tuberculosis, diabetes mellitus, bilateral cataracts, and severe degenerative joint disease of the spine. Uric acid crystals were identified in the synovial fluid. He responded well to antigout medication in spite of his age. E. D., an 86-yr-old black male, was first seen in the arthritis clinic in 1970. A review of the records showed that, in 1930, his blood sugar was as high as 600 mg/lOO ml, and urinalysis showed a urinary tract infection. Later, tubercle bacilli were recovered from gastric washings. Serum creatinine was I .3 mg/lOO ml, the hematocrit 35%. and albumin was present in the urine. Persistent elevation of the BUN was attributed to an enlarged prostate; the blood urea was 38 mg/ 100 ml and uric acid 12.0/ 100 ml. X-rays of the chest showed no evidence of chronic lung disease, although markings were slightly increased. He was placed on colchicine, I.5 mg, and allopurinol, 300 mg, a day. When he stopped the medicine, pain in his feet, wrists, or elbows returned. Uric acid crystals were recovered from joint fluid, and from a small tophus on the left forearm. Recent studies showed the blood urea to be 18 mg/lOO ml and the uric acid to be 6.4/mg 100 ml.

Another black male had several uric acids that were in the normal or high normal range, clinical symptoms suggestive of rheumatoid arthritis, a negative RA latex, and a satisfactory response to antigout drugs. Although he denied using diuretics, it was eventually discovered that he had received thiazides sometime prior to his initial bout of gouty arthritis. M. F., a 66-yr-old black male whose mother was Indian, was first seen in the clinic with a 4-yr history of intermittent attacks of joint distress, monoarticular and polyarticular, of ankles, knees, hands, and great toes. The serum uric acid, before antigout medication, varied between 4.7 mg and 7 mg/lOO ml. He responded poorly to a full course of colchicine, and, when he responded nicely to butazolidine later, the possibility of rheumatoid arthritis was entertained. The RA latex test, however, was negative. At the initial examination he denied having a high blood pressure in the past, but when his blood pressure was found to be 195/90, he admitted using chlorothiazide, methyldopa, and digitoxin before his first attack of acutegouty arthritis. He was placed on colchicine, 1.5 mg, and allopurinol, 300 mg a day. When he took these medicines, his gout was kept under control. The first x-rays of the feet showed marked irregularity of some of the margins and spur formation, particularly on the left. Aspiration of the ankle showed urate crystals, and the diagnosis of gout seemed firm. A diagnosis of pyelonephritis was interpreted from changes on

236

the intravenous pyelogram. 5.5 mg to 9.4 mg/lOO ml.

TALEOTT

The blood urea was 16 mg/lOO

ml. Recent

ET AL.

serum uric acids varied from

Another black male was thought to have rheumatoid arthritis for the first 4 yr of his clinical course, but the serology was weakly positive, and the serum uric acid elevated. Tophi appeared eventually, and a firm diagnosis of gout appeared justified. He responded well to antigout drugs in spite of excessive intake of alcohol. C. P., a 48-yr-old black male, had arthritis for more than 7 yr. highly suggestive of RA, but later suggestive of gouty arthritis. He had an Indian grandmother. Some attacks lasted more than one wk, involving feet and knees. The ANA test was negative, and the RA latex was weakly positive. Serum uric acids were as high as 14 mg/lOO ml. Hemoglobin was 11.6 g/100 ml and urine negative for albumin. For the past 3 yr he has had intermittent arthritis of the hands, knees, elbows and feet, and has complained of symmetrical morning stiffness. For a month, he had suffered from bilateral swelling of the lateral aspects of both feet, and was no longer able to walk. On physical examination, the metatarsophalangeal joints were swollen, hot and tender, with tophi on the lateral aspects of both feet. The knee showed an effusion, with warmth, tenderness, and crepitus. Fluid aspirated from the left knee showed many uric acid crystals, which confirmed the diagnosis of gout. The patient was started on protnmecid and indomethacin; later this was changed to colchicine, 1.0 mg, and allopurinol 300 mg/day. These drugs controlled the arthritis. Serum uric acid was 8.8 mg/ 100 ml on medication. He continued a high consumption of alcohol, but the arthritis remained under control. X-rays of both knees showed marked destruction, bilaterally; x-rays of the feet showed bone destruction of the proximal phalanx of the right great toe consistent with gout.

Another black male had a lo-yr history of high blood pressure, gouty arthritis, and a somewhat higher concentration of hemoglobin than usually seen in this clinic. Uric acid crystals were recovered from the joint fluid. He had not received thiazide drugs pnor to his acute attacks of gouty arthritis. J. J., a 37-yr-old black male whose grandmother was Indian, had a IO-yr history of intermittent attacks of acute gouty arthritis and hypertension, which was recognized after the initial attack of gout. He is the youngest patient in our series of gout. Blood pressures were as high as 210/140, but he denied having taken diuretics, and nothing in the record indicated that he had received thiazides or other drugs sometimes associated with hyperuricemia. Joint involvement included the great toes and knees, with obvious tophi on the feet. Uric acid crystals were identified in the fluid from the right knee. Serum uric acid varied from 8.6 mg to 12.6 mg/lOO ml. The hemoglobin was 17.7 g/100 ml and hematocrit 64%. Urine showed I+ albumin. Excessive alcoholic intake had been a problem at times. The several usual, as well as unusual, causes of polycythemia were explored and found lacking. The hypertension was thought to follow gouty arthritis, and the relatively high serum uric acid of 12.6 mg/ 100 ml is not an uncommon finding in young males with gout. X-rays of the feet were interpreted as osteoarthritis rather than gouty arthritis, but characteristic cystic lesions of gouty arthritis were evident. He responded well to colchicine I.0 mg and allopurinal 300 mg aday. DISCUSSION

This review of 65 cases of gout in blacks is presented to emphasize the relatively higher incidence of gout in this race than is commonly held. Accurate data of the ratio of gout among whites and blacks was not the purpose of this study, but we believe that the blacks may comprise as many as one-third of all gout patients in the clinics sampled. The introduction of the several thiazide drugs into clinical medicine, drugs that elevate the serum uric acid level, adds to the number of new cases of gout. However, sickle cell disease and sarcoidosis, two conditions

GOUTY ARTHRITIS

237

IN BLACK RACE

Table 1.

Clinical Data Male

Female

43

22

26

34

Oldest, at age of onset (yr)

72

80

Oldest living (yr)

86

81

6

0

Indian ancestry

13

9

Sickle cell trait

1

2

Subject Number

of patients-Total

Youngest,

Family

at age of onset (yr)

history of gout-positive

with a predilection for blacks, were not factors in any of these cases of gout, nor were there any examples of gout secondary to a blood dyscrasia. One would have expected that in a series of 65 cases, there might be as many as 10% whose gout could be attributed to a blood dyscrasia. IQFurthermore, only one patient in the series suffered from pulmonary tuberculosis. He had long since recovered before his attacks of gout appeared, and it could not be determined whether he had ever received pyrizinamide, one of the drugs known to produce hyperuricemia. The youngest patient in the series (J. J.) had his first attack of gout at the age of 27, while the oldest patient, a male (E. D.) 87 yrs, developed gout 40 yr earlier (Table 1). The oldest female was 83 yr. She had osteoarthritis and some evidence of rheumatoid arthritis, but the symptoms of acute gouty arthritis appeared only after she had been given thiazides. One patient, G. R., was the only female who had delivered a living child, now 1I yr old. This is an unusual case and has not been reported in the literature. The few that admitted to a family history of gout are of no demographic value because of the unreliability of such data in the group studied. The distribution of males versus females 43:22 is a considerably higher ratio of females than most series (Table 2). Uric acid crystals were recovered and identified either from a tophus or, more often, synovial fluid from the majority of patients (Table 2). The response to a full course of colchicine was eventually successful in all patients in whom the opportunity to determine its response was given. Renal calculi were present in one male only. This is unusual when compared with a 15%-20% incidence usually reported. The presence of hypertension and albuminuria were noted in approximately 50% of the patients. Osseous tophi were suspected by x-ray in 50% of the patients, and a smaller number showed subcutaneous tophi (Fig. 32). The onset of acute gout was identified with the toe or foot in slightly more than 50% of the patients. Table 2. Subject

Clinical Findings MaIs

Female 22

Number

43

Onset in toe or foot

24

11

Uric acid crystals identified

41

19

Subcutaneous

18

3

Hypertension

21

11

klbuminuria

23

10

Osseous tophi

17

17

1

0

Renal calculi

tophi

238

TALBOTT

ET AL

Fig. 32. Extensive tophaceous changes in a 68-y-old who suffered from polyarticular distress for many years and tophaceous deposits for at least 15 yr. Treatment was sporadic at all times.

The associated diseases were somewhat higher than other series (Table 3). Several had diabetes mellitus,23 usually mild. Other diseases sometimes associated with gout were not observed. Among the joint conditions, degenerative joint diseases was encountered frequently, but it probably made no significant contribution to the overall clinical management of gout. Rheumatoid arthritis, on the other hand, can not be dismissed so easily. This was a frequent diagnosis entered in the chart, usually by a staff physician not on the arthritis service. Sometimes the patient complained of morning stiffness as well as polyarthritis, and, if the diagnosis of gout had not been confirmed, a presumptive clinical diagnosis of RA, without laboratory confirmation, might have been justified. There remains one other factor pertinent to this series of gout cases, and that is the role of renal dysfunction and hypertension associated with hyperuricemia. I (JHT), believe and have stated for decades, that the number of cases of gout secondary to chronic renal disease, usually chronic glomerular nephritis, is extremely small. When well-developed renal disease is seen in patients with gout, it is secondary to the gout and not visa versa. However, hyperuricemia with crystal deposition in the renal parenchyma, and subsequent renal insufficiency or deposition of urate crystals with urate stone formation, may provide a fertile field for infection.24 A firm diagnosis of pyelonephritis was made in four patients. Table 3.

Number Suspicion

of rheumatoid

Degenerative

arthritis

Other

Diseases

43

22

7

2

15

11

joint disease on

x-ray or clinical findings Diabetes mellitus-all Sickle cell disease

mild

6

1

0

0

GOUTY ARTHRITIS

239

IN BLACK RACE

There were no recognized instances of saturnine gout in this series. We are aware of the subtle development of gout among chronic drinkers of moonshine whiskey, distilled in lead containers. No systematic study of lead excretion in these series was done. However, moonshine usually is not common in southern Florida. Furthermore, this possibility was explored by one of us (NG) several years ago, and no excess urinary excretion of lead was detected in a small group of patients with gout, following procedures for mobilization of lead. SUMMARY

This review of 65 black-black patients with gout, in contrast to tan or tinted, is presented to emphasize the universal nature of the disease, irrespective of race or geographic region. One case of a female who delivered a living child 4 yr after her initial attack of gout is reported. No case of gout secondary to chronic renal disease, or to a blood dyscrasia, including sickle cell disease, was discovered. Except for the race, aberrant sex distribution and low incidence of urate stones, this series is not unlike a series of white gout patients. REFERENCES 1. Hench Sixth

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