Clin. Radiol. (1975) 26, 27-36 THE
RADIOLOGY
OF GOUT
REVIEW ARTICLE IAIN WATT and H O W A R D MIDDLEMISS
From the Departments of Radiology, The University of Bristol, and the United Bristol Hospitals, Bristol The radiological features o f gout are presented on the basis of a consecutive series of 64 in-patients and a review of the literature. Gout is a painful and potentially crippling disorder. Since fewer patients are referred with a classical acute attack due to the advent of more effective drug therapy, the radiologist may be presented with unusual or atypical cases. It is confirmed that there are no specific radiological features of gout. Provided a high index of suspicion be maintained, particularly in those groups of patients in whom secondary gout is common, a combination of signs may allow the diagnosis to be correctly inferred, leading to biochemical confirmation.
CLINICAL FEATURES
GOUT was originally called Podagra from the Greek Pous, meaning foot and Agra attack. The term at present in usage has been adapted from the Latin Gutta, which refers to 'a defluxion of the humors'. Gout is honoured in antiquity and its history is as long as that of medicine itself. A large mass was described in the great toe of the skeleton of an elderly male in a cemetery in upper Egypt by Smith and Jones (1910), and one of the oldest renal calculi was recovered from an Egyptian mummy dating from about 5000 B.C., containing a uric acid nucleus (Kittredge and Downs, 1952). The Ebers papyrus of about 1500 B.C. records the prescription of colchicum and describes arthritis of the great toes. Hippocrates, the father of modern medicine (460-370 B.C.), gave a classical description of the 'unwalkable disease', and Hieron of Syracuse (400 B.C.) described a joint disease associated with bladder stones. Nearly 2000 years later uric acid was first identified in the urine of a patient with gout (Scheele, 1776), from an author's ear tophus (Wollaston, 1797) and from the blood of a patient by Garrod (1848). William Cullen (1778), sometime Professor of Medicine in both Edinburgh and Glasgow in the eighteenth century, commented that gout afflicted the wise, and Talbot (1967) quotes an impressive list of famous patients suffering with the disease, including Darwin, Harvey, Hunter, Newton and Sydenham. The first radiological manifestation of the disease was documented by Huber (1896) shortly after the discovery of X-rays.
It has become equally time-honoured that the disease shows its major manifestations in men of middle age with large frames, vigorous appetites, leading sedentary lives (Brailsford, 1959). This concept has been refuted of recent years (Talbot, 1967) and it has been shown that a purine-free diet reduces the serum uric acid by u p to 1 mg per 100 ml (Watts, 1973). However, hyperlacticacidaemia from excessive alcohol intake may precipitate acute gout in patients with hyperuricaemia (Watts, 1973). In the 64 patients examined in the present series, 22 % had a history of excessive alcohol intake. Gout afflicts 0'3 % of the general population in Europe and the United States of America, and causes 0.7 % of loss of days work due to rheumatic disorders (Dixon, 1972). The disease accounts for about 5 % of all patients suffering from arthritis (Hench, 1935). The predominant feature of gout is arthritis involving usually the small joints of the extremities and occurring in crises, which are usually associated with hyperuricaemia. There is a familiatendency. The attacks are the result of the deposil tion of crystals of monosodium urate monohydrate (MSU) in synovial cavities. It is probable that MSU injures leucocytes by interacting with lysosomes formed in response to phagocytosis of the crystals. The lysosomes whose membranes contain oestradiol are not susceptible to MSU, whereas testosteronecontaining lysosomes are (Weissman and Rita, 27
28
CLINICAL RADIOLOGY
1972). This may partly explain the male predominance of the disease. Further preliminary data from the same authors have shown that when liposomes are made omitting cholesterol they are resistant to damage by MSU, offering a possible explanation for the susceptibility to gout in the obese. Many precipitating factors have been incriminated for the acute attack. Focal trauma may explain the less common sites of acute gouty arthritis seen occasionally, for example in joiners (the hands), treadle workers (the ankles) and motor drivers (the knee or hip). A direct blow upon the joint may be followed by an acute attack (Copeman, 1969). Chronic deposition of MSU occurs in the form of tophi which contain a matrix of protein, lipid and polysaccharide material surrounded by a foreign body reaction. They occur close to joints in the sub-articular regions of bones, in bursae and tendon sheaths, and in articular cartilage. Subcutaneous tophi may eventually ulcerate through the skin and discharge fluid containing gritty particles of MSU. It has been estimated that, overall, 45 % of patients with overt gout develop t0phi (McCracken et aL, 1946), and that in about 5% of patients the tophi attain sufficient size to inhibit joint movement and seriously cripple the patient (Talbot, 1949). There are many causes of hyperuricaemia and gout (Table 1). Certain features, however, distinguish between primary and secondary gout (Table 2). Primary gout rarely afflicts females, figures of about 4% being common in the world literature
(Talbot, 1967). However, in secondary gout the proportion of female patients is 30%; there is a fourfold increase in the number of urate calculi; the joint of presentation may be atypical; and the formation of tophi may precede the initial acute attack. The radiological manifestations of primary and secondary gout are, however, identical (Lambeth et al., 1970). The joints most commonly afflicted by primary gout are the toes, ankles, knees, wrists, fingers and elbows, in that order (Talbot, 1967). Scudamore (1823) showed that 60 % of his patients had attacks initially in the great toes unilaterally, and a farther 5 % bilaterally. The present series confirms this distribution, attacks in the great toes occurring four times more commonly than in any other joint. Acute polyarthritis was only seen in one patient, who had primary gout, RADIOLOGICAL FEATURES A. Acute Gout. - in acute gout the only commonly found sign is soft-tissue swelling. However, particularly in secondary gout, previous subclinical attacks may leave stigmata of chronic gout, either at the site of the acute attack or elsewhere. B. Chronic Gout. - The manifestations of chronic gout are consequent to the tophaceous deposit of MSU. Soft-tissue swelling may be found around afflicted joints due to para:articular deposition of MSU or involvement of bursae. Particular sites are the olecranon and the Achilles tendon. Bilateral involvement of the olecranon is classical, giving
TABLE l
TABLE 2
CONDITIONS ASSOCIATEDWITH HYPERURICAEMIA
DIFFERENTIAL FEATURESOF PRIMARY AND NECONDARY G o u t
Essential hyperuricaemia and idiopathic gout Myeloproliferative diseases and reticuloscs Chronic haemolytie states, glucose-6-phosphate deficiency Psoriasis Drug treatment, e.g. diuretics and salicylates Starvation, acute alcoholism and ketoacidosis Down's syndrome Hypertension and toxaemia of pregnancy Thyroid and parathyroid disease Chronic glomerulonephritis, chronic pyelonephritis Nephrogenic diabetes insipidus Lesch - Nyhan syndrome
(A more detailed list is cited by Watts (1973))
Feature
Prhnary 40 years
Age of onset
(average) 4%
Female patients Mean serum uric acid
Tophi Family history
54 years
(average) 30%
9.ling
12 mg
11% Toes, ankles, knees, etc. Follow onset of acute attacks
40%
(SUA) Urate ealculi Joints afflicted
Secondary
25% After G u t m a n (1953)
Atypical May precede acute attacks None
29
THE R A D I O L O G Y OF GOUT
rise to a well-defined crescentic soft-tissue mass described as the 'rising sun appearance' by Wright (1966). Soft-tissue tophi rarely calcify, and it has been suggested that the presence of calcification suggests the possibility of a co-existing abnormality of calcium metabolism (Jacobs, 1973). Erosions are one of the hallmarks of gouty arthropathy, and were the first described sign of gout (Huber, 1896). The erosions are classically 'punched out', round or oval, in the long axis of
the bone (Fig. 1). They may be symmetrical and have a well-defined sclerotic rim. They vary in size from 1 m m to as much as 3 cm, but larger involved areas are probably produced by coalescence. It has been claimed that the size of the lesion is important, since other arthritides may produce similar lesions, but areas of absorption larger than 5 m m are suggestive of gout (Wright, 1966). The erosions are certainly not diagnostic (McClure and McCarty, 1919). They may be multiple and coalesce to
FIG. 1 Sharply demarcated oval erosion in the head of the first metatarsal. Male, 61 years, gout secondary to essential hypertension on diuretics for eight years. Urea 113 mg/100 ml. SUA l l . 2 m g / 1 0 0 m l .
Multiple confluent erosions around the ring and little finger metacarpo-phalangeal joints presenting a honeycomb
FIG. 2
appearance. Male, 56 years, 36-year history of primary gout.
30
CLINICAL RADIOLOGY
present a honeycomb appearance (Fig. 2 ) and, when related to the articular surface of an afflicted joint, predispose to subchondral collapse. Coexisting destruction of articular cartilage from urate deposit causes the early development of secondary degenerative osteoarthrosis (Lichtenstein e t al., 1956) (Fig. 3). When an erosion is present at the periphery of the bone it may give rise to an elevated bone margin, characteristically with a shell-like configuration, occurring most commonly in the hand or foot (Figs. 4, 5). This was described as the 'overhanging margin' of bone by Martel (1968), being present in about 40 % of his patients. Soft-tissue tophi may cause pressure defects in the underlying bone (Fig. 6). Multiple pressure defects may cause considerable waisting of bone (Fig. 7) and this is one of the recognised causes of 'vanishing bones' (Wright, 1966). Spurs and exostoses at other sites are more frequently found in patients with gout at the sites of muscle and tendon insertion (Wright, 1966). They are commonly seen in the fingers, os calcis, patellar insertions of quadriceps and pateUar tendon. They may occasionally present bizarre appearances (Figs. 8, 9). Ossification of tophi undoubtedly occurs, and it has been the experience in t h e present review that they most commonly do so in the para-
articular region. The development of cancellous bone within the tophus is initially separate, eventual integration into the underlying bone occurring, with resorption of the old cortex (Figs. 10, 11). Periosteal new bone formation is unusual, and if it occurs is often limited to such manifestations as the overhanging margin of bone. Occasionally periosteal new bone may spread along the shaft of a tubular bone, or be found as irregular new bone formation involving particularly the medial cuneiform (Fig. 12). It may occasionally be extensive (Fig. 13). Osteoporosis may occur rarely in the acute attack, although it is said by Staple (1971) to be common. Osteoporosis is seen in the chronic condition purely as the result of disuse. Wright (1966) described three cases of clinically proven gout associated with Paget's disease. It is interesting to note that Paget (1882) in one of his early papers on osteitis deformans described seven cases of gout, five of which had a history or family history of gout, and suggested there may be an association between the two conditions. No example has been seen in this series. Chondrocalcinosis has been reported to occur in about a third of patients with gout (Staple, 1971 ; Dodds and Steinbach, 1966). However Good and Rapp (1967), in a controlled series, found
FIG. 3
FIG. 4 Multiple overhanging margins of bone and exostoses, proximal interphalangeal joints of middle and ring fingers. Male, 54 years. 30-year history of primary gout.
Subchondral collapse with secondary osteoarthrosis, metacarpo-phalangeal joints of index and middle fingers. Same patient as Fig. 2.
THE R A D I O L O G Y OF GOUT
Fro. 5 Overhanging margin of bone, middle phalanx of ring finger. Multiple marginal tophi and asymmetrical soft tissue swelling. Male, 68 years. Primary gout also treated with diuretics for congestive heart failure. 20-year history. SUA 11.5 mg/100 ml. Urea 60 rag/100 ml. FIG. 6 Marked smooth erosions of the ulnar styloid by soft-tissue tophi. Male, 45 years. Primary gout.
31
Fro. 7 Marked waisting of the middle phalanx of the index finger due to multiple tophi. Bony ankylosis of the proximal interphalangeal joint, multiple exostoses and ossifying tophi are present. Male, 78. Primary gout. Fro. 8 Bizarre symmetrical exostoses around the proximal interphalangeal joints of the index finger. Female, 68 years. Gout secondary to chronic pyelonephritis and hypertension.
32
CLINICAL RADIOLOGY
! I
i
i V
Fin. 9 Large exostosis of the ulnar styloid (there were bilaterally symmetrical lesions): Male, 40 years. Long history of primary gout.
FIG. 11 Ossified tophi. The underlying cortex of the proximal phalanx remains intact. Same patient as Fig. 9.
Fro. 10 Ossified, integrated, tophi adjacent to the proximal interphalangeal joint of the ring finger. Subchondral collapse of the corresponding joint of the little finger. Male, 71 years. Polycythaemia rubra vera for 25 years. Gout for seven years.
F1G. 12 Periosteal new bone with so~-tissue swelling overlying the medial cuneiform. Male, 72years. Primary gout for ten years.
THE
RADIOLOGY
OF
GOUT
33
Fro. 13 (above) Extensive periosteal new bone along the shaft of the right first metatarsal, A discrete erosion of the metatarsal head is present. Male, 63 years. Acute gout following diuretics for acute heart failure after a myocardial infarction.
F~G. 14 (right) Right unilateral thoracic spondylosis. Male, 64 years. Primary gout and late-onset diabetes mellitus. chondrocalcinosis in about 5 ~ of patients with gout and about 8 ~ of patients with rheumatoid arthritis. They concluded that there was no particular association between gout and chondrocalcinosis. Chondrocalcinosis is a recognised manifestation of pyrophosphate arthropathy, which Martel et al. (1970) claim has a distinct radiological appearance compared with gout. The present writers have been unable to recognise this distinction: certainly these two causes of crystal synovitis
may co-exist and both respond to colchicum. It is therefore not clear whether or not chondrocalcinosis occurs as a primary manifestation of gout. It may be that arthroscopy may provide a definitive differential diagnosis (Dixon, 1972). Right unilateral thoracic spondylosis was initially described as the 'sugar glazed spine' by Wenzel (1824). Anterior ribbon-shaped ossification in the thoracic spine has been significantly linked with diabetes and sub-clinical diabetes by Schoen (1970),
34
CLINICAL RADIOLOGY
confirming the earlier observations by H/tjkov~t et al. (1965). Tkach (1970) reviewed the spinal manifestations of patients with gout and noted an association with unilateral thoracic osteophytosis in some of their patients. The aetiology is unknown. There is no correlation between right or left handedness, osteoarthrosis elsewhere, aortic position, blood pressure, occupation or with clinical symptoms. The new bone arises in the perivertebral fibrotic sheath (Schorr et al., 1956). Ishmael (1948) reported a familial inter-relationship between gout, diabetes and obesity, and it would appear there is a strong correlation between these diseases and hyperostotic spondylosis. 7 . 8 ~ of patients with gout in the present series were found to have sub-clinical diabetes, and in the one patient in whom views of the thoracic spine were available, right unilateral spondylosis was present (Fig. 14). It is interesting to note that osteophytic bridging was present in the cervical and thoracic spine in the case documented by Brailsford (1959). Sacro-iliitis is said to occur with typical gouty changes in 7-4~ of patients. Non-specific degenerative changes are found in a further 5.3 ~ according to Lambeth et al. (1970), who describe gouty involvement of the sacro-iliac joints with large sclerotic rimmed erosions in patients with haemoglobin E and hypersplenism. Avascular necrosis of the femoral head in gout
FIG. 15 Gross bony ankylosis throughout the carpus, inferior radio-ulnar joint and some of the carpo-metacarpal joints. There are multiple large erosions in the distal radius and ulna. Same patient as Fig. 7.
is unusual. A case of apparently spontaneous avascular necrosis was reported by Hunder et al. (1968). At operation the hyaline cartilage was encrusted with urate deposits. It would seem that about 4 to 5 ~ of patients with avascular necrosis of the hip have hyperuricaemia or frank gout. However, the accelerated osteoarthrosis associated with gout may contribute a further percentage of cases, being indistinguishable from primary avascular necrosis. Bony ankylosis. The usual long-term complication of the secondary osteoarthrosis found in gouty arthropathy is fibrous ankylosis. Bony ankylosis has only been described three times in the literature (Ludwig et al., 1938; Dixon, 1967; Hughes et al., 1968). A further four cases have been seen in this present review (Fig. 15), all in patients with advanced, crippling gout. Acute obstructive uropathy from urate calculi may initially be the clinical presentation of patients both with primary and secondary gout. Radiological examination of the hands and feet in a patient with a calculous obstruction may reveal a gouty diathesis. Peripheral arterial calcification was described by Brailsford (1959) in a case report of a patient with gout. This phenomenon has been seen in a further three patients in the present review and in all there was associated diabetes mellitus. It seems possible, therefore, that peripheral arterial calcification in patients with gout is the result of the co-existing diabetes. C . J u v e n i l e G o u t . - The development of gout in a child is rare. The earliest reported case was in a 5-week-old infant without a family history (Schopf, 1930). Only two cases are reported in the radiological literature. An 8-year-old male presenting with joint space narrowing, sub-cortical bone destruction, absorption of the tips of the terminal phalanges, progressive soft-tissue calcification, osteoporosis and epiphyseal growth disturbances was reported by Middlemiss and Braband (1962). Wright (1966) reported a boy of 15 with speckled calcification, destruction and disintegration of the epiphyses of the proximal phalanges at both first metatarsophalangeal joints. Primary gout has been reported in a 3-year-old girl by Rausch (1950). In the younger onset group it would appear that the principal differential diagnostic pitfall is juvenile rheumatoid arthritis (Middlemiss and Braband, 1962), and that in the early stages the diagnosis may only be established chemically. The later manifestations, for example
THE R A D I O L O G Y OF GOUT
erosions, may radiologically.
suggest the diagnosis of gout
DISCUSSION Gout remains a slightly humorous subject with overtones of surfeits of port and good living. It is however, to the sufferer, a painful and crippling disorder- It remair~s a subject of controversy with regard to its ultimate morbidity and mortality. Earlier reports (Talbot, 1949) emphasise the constancy of renal complications of the disease, but in a later report (Talbot, 1967) on a small series, no excess mortality was found. Hall (1965), on data from the Framingham Study, showed that gouty patients are more prone to develop coronary artery disease than non-gouty patients. Ungerleider (1954), in a review of life insurance tables, however, believed that longevity of patients with gout was not compromised. Modern anti-gout therapy may well influence the outcome. Tophaceous deposits will gradually resolve provided that good biochemical control is maintained, but it needs to be life-long. Deposits of mono-sodium urate can be mobilised from the renal substance and stone formation stopped. The effects of associated renal inflammation and fibrosis cannot be repaired and overall renal function, if already compromised, remains unchanged (Watts, 1973). Many patients with classical acute gout no longer reach hospital consultation (Jayson, 1973), and the radiologist is presented often with difficult and unusual problems. Indeed the incidence of primary gout in this present study was only 56 of cases, and gout secondary to renal failure and/or hypertension was found in 2 2 ~ . 6 ' 2 5 ~ were secondary to blood dyscrasias, a figure of 10~ being quoted by Watts (1973). 42 ~ of the present cases had acute attacks following the use of diuretics, the risk of which was stressed first by Radcliffe (1716). Psoriatic arthropathy may be difficult to differentiate radiologically since there is a high incidence of hyperuricaemia in patients with psoriatic arthropathy, with an association with frank gout (Eisen and Seegmiller, 1961). The raised serum urate level is thought to be due to increased nucleic acid turnover resulting from accelerated epidermal cell proliferation, and may return to normal levels after clinical remission of the skin condition (Copeman, 1969). The subchondral collapse from gout may produce the 'arrowhead' deformities commonly seen in psoriasis. Bony ankylyosis may occur in both conditions. However, in psoriasis the
35
soft-tissue swelling is Symmetrical and associated with juxta-articular osteoporosis. The exclusion of gout in a patient with psoriasis may depend on biochemical confirmation. The possibility of gout in acute obstructive uropathy should be borne in mind. It has been suggested, although not proved, that acute renal failure might occasionally be produced by the deposition of uric acid crystals following the use of radiological contrast media when given in single large doses (Mudge, 1971; Postlethwaite and Kelley, 1971). It is not clear whether the acute deposition of uric acid is a response to the contrast medium or of the dehydration often employed prior to excretion urography. No example has been seen in the present series. The index of suspicion for the diagnosis of gout is generally low both clinically and radiologically, a point emphasised 27 years ago by McCracken et al. (1946). It is accepted that the radiological changes of gout occur late and are often nonspecific (Copeman, 1969), and Golden (1956) suggests that only one-third o f advanced cases show sufficient characteristic radiological evidence to allow a diagnosis to be made. However, the radiologist is in a position, not only to raise the possibility of the diagnosis, but to demonstrate its extent and severity. Special consideration should be given to patients with unusual osteophytosis or degenerative osteoarthrosis with 'cyst' formation, and to patients with diseases in which the incidence of secondary hyperuricaemia is high. REFERENCES BRAILSFORD, J. F. (1959), The radiology of gout. British Journal of Radiology, 32, 472-478. COP£MAN, W. S. C. 0969) (ed.). Textbookof Rheumatic Diseases, p. 456. Livingstone. CULLEN, W. (1778). First Lines in the Praetice of Physic,
2nd edn, Vol. 1. Creech, Edinburgh. DIxoN, A. ST. J. (•967). Personal communication quoted in Hughes et aL, 1968. DIXON,A. ST. J. (1972). Recent trends. Medicine, Section 1, p. 9. London Medical Education (International) Ltd. DODDS, W. J. & STEIN'BACH,[-I. L. (1966). Gout as associated with calcification of cartilage. New England Journal of Medicine, 275, 745-749.
EISEN, A. Z. & SEEGMILLER,J. E. (1961). Uric acid metabolism in psoriasis. Journal of Clinical Investigation, 40, 1486-1494. GARROD,A. B. (1848). Observations on certain pathological conditions of the blood and urine in gout, rheumatism and Bright's disease. Transactions of Medical and Chirurgical Society, ¥ol. 31, p. 85, GOLDEN, R. (1956). Diagnostic Roentgenology, Part 2, pp. 5550-5553. Williams and Wilkins, Baltimore. GOOD, A. E. & RAPP, R. (1967). Chondrocalcinosis of the
36
CLINICAL RADIOLOGY
knee with gout and rheumatoid arthritis. New England Journal of Medicine, 277, 286-290. GUTMAN, A. B. (1953). Primary and secondary gout. Annals of lnternal Medicine, 39, 1062-1076. HAJKOVA.,Z., STREDA, f . & SKRttA, F. (1965). Hyperostoti spondylosis and diabetes mellitus. Annals of Rheumatic Diseases, 24, 536-543. HALL, A. P_ (1965). Correlations among hyperuricemia, hypercholesterolemia, coronary disease and hypertension. Arthritis and Rheumatism, 8, 780~795. HUNCH, P. S. (1935). A clinic on some diseases of joints. Medical Clinics of North America, 19, 551-583. HUBER, (1896). The use of x-rays in internal medicine. Deutsche Mediziuische Wochenschrift, 22, 182195. HUGHES, G. R., BARNES, C. G. & MasoN, R. M. (1968). Bony ankylosis in gout. Annals of Rheumatic Diseases, 27, 67-70. HUNDER, G. G_, WORTHINGTON, J. W. & BICKEL, W. H. (1968). Avascular necrosis of the femoral head in a patient with gout. Journal of the American Medical Association, 203, 101-103. ISHMAEL, W. K. (1948). The familial aspects of gout, diabetes mellitus and obesity. Journal of the Oklahoma State Medical Association, 38, 415-423. JacoBs, P, (1973). Atlas of Hand Radiographs, p. 248. Harvey Miller and Medcalf, London. JAYSON, M. I. V. (1973). Personal communication. KITTREDOE, W. E. & DOWNS, R. (1952). The role of gout in the formation of urinary calculi. Journal of Urology, 67, 841-847. LAMBETH, J. T., BURNS-Cox, C. J. & MACLEANR. (1970). Sacroiliac gout associated with haemoglobin E and hypersplenism, Radiology, 95, 413M15. LICHTENSTEIN, L., SCOTT, H. W. & LEVIN, M. [-:[. (1956). Pathologic changes in gout: survey of 11 necropsied cases. American Journal of Pathology, 32, 871-895. LUDWIG, A. O., BENNETT, G. A. & BAUER, W. (1938). A rare manifestation of gout; widespread ankylosis simulating rheumatoid arthritis_ Annals of lnternal Medicine, 11, 1248-1276. MARTEL, W. (1968). The overhanging margin of bone; a roentgenologic manifestation of gout. Radiology, 91, 755-756. MARTEL, W., KOHLER, C- C., THOMSON, G. R. & CARTER, T. L. (1970). A roentgenologically distinctive arthropathy in some patients with the pseudogout syndrome. American Journal of RoentgenolOgy, 109, 587-607. McCLURE, C. W. & MCCARTY, E. D. (1919). Roentgenographic studies in gout. Archives of Internal Medicine, 24, 563-579. MCCRAC~N, J. P., OWEN, P. S. & PRATT, J. H. (1946), Gout; still a forgotten disease. Journal of the American Medical Association, 131, 367-372. MmDLEMrSS, J. H. & 'BRABAND, H. (1962). Juvenile gout. Clinical Radiology, 13, 149-152.
MUDGE, G. H, (1971). Uricosuric action of cholecystographic agents. A possible factor in nephrotoxicity, New England Journal of Medicine, 284, 929-933. PAGET, SIR J. (1882). Additional cases of osteitis deformans. Medico-Chirurgical Transactions, 65, 225-236. POSTLEXHWAITE,A. E. & KELLEY, W. N. (1971). Uricosuric effect of radio contrast agents. A study in man of four commonly used preparations. Annals of Internal Medicine, 74, 845-852. RADCLIFF, J. Quoted in STRUTHER,E. (1716). Dr Radchff's Practical Dispensary containing a Complete Body of Prescriptions Fitted for all Disease, Internal and External Digested under Proper Heads. Rivington, London. RAUsc~, W. M. (1950). Gout in a girl 3½ years old. Medizinische Monatsshrift (Stuttgart), 4, 931-933. SCHEELE, K. W. (1766). Chemical examination of urinary calculi_ Opuscula, 2, 73. SCHOEN, D_ (1970). Hyperostofic spondylosis and diabetes mellitus. Symposium Ossium, ed. Jelliffe, A. M. & Strickland, B., pp. 175-177, E. Livingstone, Edinburgh and London. SCHOPF, E_ M. YON (1930). Gout in a five-weeks-old infant_ Klinische ~Fochenschrift, 9, 2148-2151. SCHORR, S., FR,KNKEL, M. & ADLER, E. (1956). Right unilateral thoracic spondylosis. Journal of the Faculty of Radiologists, 8, 59-65. SCUI)AMORE,C, (1823), A Treatise on the Nature and Course of Gout, 4th edn. Mallett, London. SMITH, G. E. & JONES, F. W. (1910). The Archaeological Survey of Nubia. Report for the 1907-8, Vol. 2, pp. 44, 269. National Printing Department, Cairo. STAPLE, T. W. (1971). Gout. Principals of Diagnostic Radiology, ed. Petchen, E. J., Koehler, P. R. & Davis, D. O., pp. 150-151. McGraw-Hill. TaLbOT, J. H. (1949). Diversity of gouty arthritis and its complications. Annals of Internal Medicine, 31, 555-569. TALBOT, J. H. (1967). Gout, 3rd ed. Grune & Stratton, New York and London. TKACH, S. (1970). Gouty arthritis of the spine. Clinical Orthopaedics and Related Research, 71, 81-86. UNGERLE~DER, H. E. (1954). Internist and life insurance. Annals of Internal Medicine, 41, 124-130. WATTS, R. W, E. (1973). Gout. Medicine, Vol. 12, pp. 783-789. London Medical Education (International) Ltd. WEISSMAN, G. & RITa, G. A. (1972). Molecular basis of gouty inflammation: interaction o f monosodium urate crystals with lysosomes and liposomes. Nature (New Biology), 240, 167-172. WENZEL, C. (1824). Cited by Schmorl, G. & Junghanns, H. (1951). Die gesunde und Kranke Wirbelsdule in Rdntgenbild und Klinik, 2nd edn, p. 209. G. Thieme, Stuttgart_ WOLLASTON,W. H. (1797). Gouty and urinary concretions. Philosophical Transactions, 87, 386-391_ W~t~GHT, J. T. (1966). Unusual manifestations of gout. Australasian Radiology, 10, 365-374.
RADIOLOGY
OF GOUT
REVIEW ARTICLE IAIN WATT and H O W A R D MIDDLEMISS
From the Departments of Radiology, The University of Bristol, and the United Bristol Hospitals, Bristol The radiological features o f gout are presented on the basis of a consecutive series of 64 in-patients and a review of the literature. Gout is a painful and potentially crippling disorder. Since fewer patients are referred with a classical acute attack due to the advent of more effective drug therapy, the radiologist may be presented with unusual or atypical cases. It is confirmed that there are no specific radiological features of gout. Provided a high index of suspicion be maintained, particularly in those groups of patients in whom secondary gout is common, a combination of signs may allow the diagnosis to be correctly inferred, leading to biochemical confirmation.
CLINICAL FEATURES
GOUT was originally called Podagra from the Greek Pous, meaning foot and Agra attack. The term at present in usage has been adapted from the Latin Gutta, which refers to 'a defluxion of the humors'. Gout is honoured in antiquity and its history is as long as that of medicine itself. A large mass was described in the great toe of the skeleton of an elderly male in a cemetery in upper Egypt by Smith and Jones (1910), and one of the oldest renal calculi was recovered from an Egyptian mummy dating from about 5000 B.C., containing a uric acid nucleus (Kittredge and Downs, 1952). The Ebers papyrus of about 1500 B.C. records the prescription of colchicum and describes arthritis of the great toes. Hippocrates, the father of modern medicine (460-370 B.C.), gave a classical description of the 'unwalkable disease', and Hieron of Syracuse (400 B.C.) described a joint disease associated with bladder stones. Nearly 2000 years later uric acid was first identified in the urine of a patient with gout (Scheele, 1776), from an author's ear tophus (Wollaston, 1797) and from the blood of a patient by Garrod (1848). William Cullen (1778), sometime Professor of Medicine in both Edinburgh and Glasgow in the eighteenth century, commented that gout afflicted the wise, and Talbot (1967) quotes an impressive list of famous patients suffering with the disease, including Darwin, Harvey, Hunter, Newton and Sydenham. The first radiological manifestation of the disease was documented by Huber (1896) shortly after the discovery of X-rays.
It has become equally time-honoured that the disease shows its major manifestations in men of middle age with large frames, vigorous appetites, leading sedentary lives (Brailsford, 1959). This concept has been refuted of recent years (Talbot, 1967) and it has been shown that a purine-free diet reduces the serum uric acid by u p to 1 mg per 100 ml (Watts, 1973). However, hyperlacticacidaemia from excessive alcohol intake may precipitate acute gout in patients with hyperuricaemia (Watts, 1973). In the 64 patients examined in the present series, 22 % had a history of excessive alcohol intake. Gout afflicts 0'3 % of the general population in Europe and the United States of America, and causes 0.7 % of loss of days work due to rheumatic disorders (Dixon, 1972). The disease accounts for about 5 % of all patients suffering from arthritis (Hench, 1935). The predominant feature of gout is arthritis involving usually the small joints of the extremities and occurring in crises, which are usually associated with hyperuricaemia. There is a familiatendency. The attacks are the result of the deposil tion of crystals of monosodium urate monohydrate (MSU) in synovial cavities. It is probable that MSU injures leucocytes by interacting with lysosomes formed in response to phagocytosis of the crystals. The lysosomes whose membranes contain oestradiol are not susceptible to MSU, whereas testosteronecontaining lysosomes are (Weissman and Rita, 27
28
CLINICAL RADIOLOGY
1972). This may partly explain the male predominance of the disease. Further preliminary data from the same authors have shown that when liposomes are made omitting cholesterol they are resistant to damage by MSU, offering a possible explanation for the susceptibility to gout in the obese. Many precipitating factors have been incriminated for the acute attack. Focal trauma may explain the less common sites of acute gouty arthritis seen occasionally, for example in joiners (the hands), treadle workers (the ankles) and motor drivers (the knee or hip). A direct blow upon the joint may be followed by an acute attack (Copeman, 1969). Chronic deposition of MSU occurs in the form of tophi which contain a matrix of protein, lipid and polysaccharide material surrounded by a foreign body reaction. They occur close to joints in the sub-articular regions of bones, in bursae and tendon sheaths, and in articular cartilage. Subcutaneous tophi may eventually ulcerate through the skin and discharge fluid containing gritty particles of MSU. It has been estimated that, overall, 45 % of patients with overt gout develop t0phi (McCracken et aL, 1946), and that in about 5% of patients the tophi attain sufficient size to inhibit joint movement and seriously cripple the patient (Talbot, 1949). There are many causes of hyperuricaemia and gout (Table 1). Certain features, however, distinguish between primary and secondary gout (Table 2). Primary gout rarely afflicts females, figures of about 4% being common in the world literature
(Talbot, 1967). However, in secondary gout the proportion of female patients is 30%; there is a fourfold increase in the number of urate calculi; the joint of presentation may be atypical; and the formation of tophi may precede the initial acute attack. The radiological manifestations of primary and secondary gout are, however, identical (Lambeth et al., 1970). The joints most commonly afflicted by primary gout are the toes, ankles, knees, wrists, fingers and elbows, in that order (Talbot, 1967). Scudamore (1823) showed that 60 % of his patients had attacks initially in the great toes unilaterally, and a farther 5 % bilaterally. The present series confirms this distribution, attacks in the great toes occurring four times more commonly than in any other joint. Acute polyarthritis was only seen in one patient, who had primary gout, RADIOLOGICAL FEATURES A. Acute Gout. - in acute gout the only commonly found sign is soft-tissue swelling. However, particularly in secondary gout, previous subclinical attacks may leave stigmata of chronic gout, either at the site of the acute attack or elsewhere. B. Chronic Gout. - The manifestations of chronic gout are consequent to the tophaceous deposit of MSU. Soft-tissue swelling may be found around afflicted joints due to para:articular deposition of MSU or involvement of bursae. Particular sites are the olecranon and the Achilles tendon. Bilateral involvement of the olecranon is classical, giving
TABLE l
TABLE 2
CONDITIONS ASSOCIATEDWITH HYPERURICAEMIA
DIFFERENTIAL FEATURESOF PRIMARY AND NECONDARY G o u t
Essential hyperuricaemia and idiopathic gout Myeloproliferative diseases and reticuloscs Chronic haemolytie states, glucose-6-phosphate deficiency Psoriasis Drug treatment, e.g. diuretics and salicylates Starvation, acute alcoholism and ketoacidosis Down's syndrome Hypertension and toxaemia of pregnancy Thyroid and parathyroid disease Chronic glomerulonephritis, chronic pyelonephritis Nephrogenic diabetes insipidus Lesch - Nyhan syndrome
(A more detailed list is cited by Watts (1973))
Feature
Prhnary 40 years
Age of onset
(average) 4%
Female patients Mean serum uric acid
Tophi Family history
54 years
(average) 30%
9.ling
12 mg
11% Toes, ankles, knees, etc. Follow onset of acute attacks
40%
(SUA) Urate ealculi Joints afflicted
Secondary
25% After G u t m a n (1953)
Atypical May precede acute attacks None
29
THE R A D I O L O G Y OF GOUT
rise to a well-defined crescentic soft-tissue mass described as the 'rising sun appearance' by Wright (1966). Soft-tissue tophi rarely calcify, and it has been suggested that the presence of calcification suggests the possibility of a co-existing abnormality of calcium metabolism (Jacobs, 1973). Erosions are one of the hallmarks of gouty arthropathy, and were the first described sign of gout (Huber, 1896). The erosions are classically 'punched out', round or oval, in the long axis of
the bone (Fig. 1). They may be symmetrical and have a well-defined sclerotic rim. They vary in size from 1 m m to as much as 3 cm, but larger involved areas are probably produced by coalescence. It has been claimed that the size of the lesion is important, since other arthritides may produce similar lesions, but areas of absorption larger than 5 m m are suggestive of gout (Wright, 1966). The erosions are certainly not diagnostic (McClure and McCarty, 1919). They may be multiple and coalesce to
FIG. 1 Sharply demarcated oval erosion in the head of the first metatarsal. Male, 61 years, gout secondary to essential hypertension on diuretics for eight years. Urea 113 mg/100 ml. SUA l l . 2 m g / 1 0 0 m l .
Multiple confluent erosions around the ring and little finger metacarpo-phalangeal joints presenting a honeycomb
FIG. 2
appearance. Male, 56 years, 36-year history of primary gout.
30
CLINICAL RADIOLOGY
present a honeycomb appearance (Fig. 2 ) and, when related to the articular surface of an afflicted joint, predispose to subchondral collapse. Coexisting destruction of articular cartilage from urate deposit causes the early development of secondary degenerative osteoarthrosis (Lichtenstein e t al., 1956) (Fig. 3). When an erosion is present at the periphery of the bone it may give rise to an elevated bone margin, characteristically with a shell-like configuration, occurring most commonly in the hand or foot (Figs. 4, 5). This was described as the 'overhanging margin' of bone by Martel (1968), being present in about 40 % of his patients. Soft-tissue tophi may cause pressure defects in the underlying bone (Fig. 6). Multiple pressure defects may cause considerable waisting of bone (Fig. 7) and this is one of the recognised causes of 'vanishing bones' (Wright, 1966). Spurs and exostoses at other sites are more frequently found in patients with gout at the sites of muscle and tendon insertion (Wright, 1966). They are commonly seen in the fingers, os calcis, patellar insertions of quadriceps and pateUar tendon. They may occasionally present bizarre appearances (Figs. 8, 9). Ossification of tophi undoubtedly occurs, and it has been the experience in t h e present review that they most commonly do so in the para-
articular region. The development of cancellous bone within the tophus is initially separate, eventual integration into the underlying bone occurring, with resorption of the old cortex (Figs. 10, 11). Periosteal new bone formation is unusual, and if it occurs is often limited to such manifestations as the overhanging margin of bone. Occasionally periosteal new bone may spread along the shaft of a tubular bone, or be found as irregular new bone formation involving particularly the medial cuneiform (Fig. 12). It may occasionally be extensive (Fig. 13). Osteoporosis may occur rarely in the acute attack, although it is said by Staple (1971) to be common. Osteoporosis is seen in the chronic condition purely as the result of disuse. Wright (1966) described three cases of clinically proven gout associated with Paget's disease. It is interesting to note that Paget (1882) in one of his early papers on osteitis deformans described seven cases of gout, five of which had a history or family history of gout, and suggested there may be an association between the two conditions. No example has been seen in this series. Chondrocalcinosis has been reported to occur in about a third of patients with gout (Staple, 1971 ; Dodds and Steinbach, 1966). However Good and Rapp (1967), in a controlled series, found
FIG. 3
FIG. 4 Multiple overhanging margins of bone and exostoses, proximal interphalangeal joints of middle and ring fingers. Male, 54 years. 30-year history of primary gout.
Subchondral collapse with secondary osteoarthrosis, metacarpo-phalangeal joints of index and middle fingers. Same patient as Fig. 2.
THE R A D I O L O G Y OF GOUT
Fro. 5 Overhanging margin of bone, middle phalanx of ring finger. Multiple marginal tophi and asymmetrical soft tissue swelling. Male, 68 years. Primary gout also treated with diuretics for congestive heart failure. 20-year history. SUA 11.5 mg/100 ml. Urea 60 rag/100 ml. FIG. 6 Marked smooth erosions of the ulnar styloid by soft-tissue tophi. Male, 45 years. Primary gout.
31
Fro. 7 Marked waisting of the middle phalanx of the index finger due to multiple tophi. Bony ankylosis of the proximal interphalangeal joint, multiple exostoses and ossifying tophi are present. Male, 78. Primary gout. Fro. 8 Bizarre symmetrical exostoses around the proximal interphalangeal joints of the index finger. Female, 68 years. Gout secondary to chronic pyelonephritis and hypertension.
32
CLINICAL RADIOLOGY
! I
i
i V
Fin. 9 Large exostosis of the ulnar styloid (there were bilaterally symmetrical lesions): Male, 40 years. Long history of primary gout.
FIG. 11 Ossified tophi. The underlying cortex of the proximal phalanx remains intact. Same patient as Fig. 9.
Fro. 10 Ossified, integrated, tophi adjacent to the proximal interphalangeal joint of the ring finger. Subchondral collapse of the corresponding joint of the little finger. Male, 71 years. Polycythaemia rubra vera for 25 years. Gout for seven years.
F1G. 12 Periosteal new bone with so~-tissue swelling overlying the medial cuneiform. Male, 72years. Primary gout for ten years.
THE
RADIOLOGY
OF
GOUT
33
Fro. 13 (above) Extensive periosteal new bone along the shaft of the right first metatarsal, A discrete erosion of the metatarsal head is present. Male, 63 years. Acute gout following diuretics for acute heart failure after a myocardial infarction.
F~G. 14 (right) Right unilateral thoracic spondylosis. Male, 64 years. Primary gout and late-onset diabetes mellitus. chondrocalcinosis in about 5 ~ of patients with gout and about 8 ~ of patients with rheumatoid arthritis. They concluded that there was no particular association between gout and chondrocalcinosis. Chondrocalcinosis is a recognised manifestation of pyrophosphate arthropathy, which Martel et al. (1970) claim has a distinct radiological appearance compared with gout. The present writers have been unable to recognise this distinction: certainly these two causes of crystal synovitis
may co-exist and both respond to colchicum. It is therefore not clear whether or not chondrocalcinosis occurs as a primary manifestation of gout. It may be that arthroscopy may provide a definitive differential diagnosis (Dixon, 1972). Right unilateral thoracic spondylosis was initially described as the 'sugar glazed spine' by Wenzel (1824). Anterior ribbon-shaped ossification in the thoracic spine has been significantly linked with diabetes and sub-clinical diabetes by Schoen (1970),
34
CLINICAL RADIOLOGY
confirming the earlier observations by H/tjkov~t et al. (1965). Tkach (1970) reviewed the spinal manifestations of patients with gout and noted an association with unilateral thoracic osteophytosis in some of their patients. The aetiology is unknown. There is no correlation between right or left handedness, osteoarthrosis elsewhere, aortic position, blood pressure, occupation or with clinical symptoms. The new bone arises in the perivertebral fibrotic sheath (Schorr et al., 1956). Ishmael (1948) reported a familial inter-relationship between gout, diabetes and obesity, and it would appear there is a strong correlation between these diseases and hyperostotic spondylosis. 7 . 8 ~ of patients with gout in the present series were found to have sub-clinical diabetes, and in the one patient in whom views of the thoracic spine were available, right unilateral spondylosis was present (Fig. 14). It is interesting to note that osteophytic bridging was present in the cervical and thoracic spine in the case documented by Brailsford (1959). Sacro-iliitis is said to occur with typical gouty changes in 7-4~ of patients. Non-specific degenerative changes are found in a further 5.3 ~ according to Lambeth et al. (1970), who describe gouty involvement of the sacro-iliac joints with large sclerotic rimmed erosions in patients with haemoglobin E and hypersplenism. Avascular necrosis of the femoral head in gout
FIG. 15 Gross bony ankylosis throughout the carpus, inferior radio-ulnar joint and some of the carpo-metacarpal joints. There are multiple large erosions in the distal radius and ulna. Same patient as Fig. 7.
is unusual. A case of apparently spontaneous avascular necrosis was reported by Hunder et al. (1968). At operation the hyaline cartilage was encrusted with urate deposits. It would seem that about 4 to 5 ~ of patients with avascular necrosis of the hip have hyperuricaemia or frank gout. However, the accelerated osteoarthrosis associated with gout may contribute a further percentage of cases, being indistinguishable from primary avascular necrosis. Bony ankylosis. The usual long-term complication of the secondary osteoarthrosis found in gouty arthropathy is fibrous ankylosis. Bony ankylosis has only been described three times in the literature (Ludwig et al., 1938; Dixon, 1967; Hughes et al., 1968). A further four cases have been seen in this present review (Fig. 15), all in patients with advanced, crippling gout. Acute obstructive uropathy from urate calculi may initially be the clinical presentation of patients both with primary and secondary gout. Radiological examination of the hands and feet in a patient with a calculous obstruction may reveal a gouty diathesis. Peripheral arterial calcification was described by Brailsford (1959) in a case report of a patient with gout. This phenomenon has been seen in a further three patients in the present review and in all there was associated diabetes mellitus. It seems possible, therefore, that peripheral arterial calcification in patients with gout is the result of the co-existing diabetes. C . J u v e n i l e G o u t . - The development of gout in a child is rare. The earliest reported case was in a 5-week-old infant without a family history (Schopf, 1930). Only two cases are reported in the radiological literature. An 8-year-old male presenting with joint space narrowing, sub-cortical bone destruction, absorption of the tips of the terminal phalanges, progressive soft-tissue calcification, osteoporosis and epiphyseal growth disturbances was reported by Middlemiss and Braband (1962). Wright (1966) reported a boy of 15 with speckled calcification, destruction and disintegration of the epiphyses of the proximal phalanges at both first metatarsophalangeal joints. Primary gout has been reported in a 3-year-old girl by Rausch (1950). In the younger onset group it would appear that the principal differential diagnostic pitfall is juvenile rheumatoid arthritis (Middlemiss and Braband, 1962), and that in the early stages the diagnosis may only be established chemically. The later manifestations, for example
THE R A D I O L O G Y OF GOUT
erosions, may radiologically.
suggest the diagnosis of gout
DISCUSSION Gout remains a slightly humorous subject with overtones of surfeits of port and good living. It is however, to the sufferer, a painful and crippling disorder- It remair~s a subject of controversy with regard to its ultimate morbidity and mortality. Earlier reports (Talbot, 1949) emphasise the constancy of renal complications of the disease, but in a later report (Talbot, 1967) on a small series, no excess mortality was found. Hall (1965), on data from the Framingham Study, showed that gouty patients are more prone to develop coronary artery disease than non-gouty patients. Ungerleider (1954), in a review of life insurance tables, however, believed that longevity of patients with gout was not compromised. Modern anti-gout therapy may well influence the outcome. Tophaceous deposits will gradually resolve provided that good biochemical control is maintained, but it needs to be life-long. Deposits of mono-sodium urate can be mobilised from the renal substance and stone formation stopped. The effects of associated renal inflammation and fibrosis cannot be repaired and overall renal function, if already compromised, remains unchanged (Watts, 1973). Many patients with classical acute gout no longer reach hospital consultation (Jayson, 1973), and the radiologist is presented often with difficult and unusual problems. Indeed the incidence of primary gout in this present study was only 56 of cases, and gout secondary to renal failure and/or hypertension was found in 2 2 ~ . 6 ' 2 5 ~ were secondary to blood dyscrasias, a figure of 10~ being quoted by Watts (1973). 42 ~ of the present cases had acute attacks following the use of diuretics, the risk of which was stressed first by Radcliffe (1716). Psoriatic arthropathy may be difficult to differentiate radiologically since there is a high incidence of hyperuricaemia in patients with psoriatic arthropathy, with an association with frank gout (Eisen and Seegmiller, 1961). The raised serum urate level is thought to be due to increased nucleic acid turnover resulting from accelerated epidermal cell proliferation, and may return to normal levels after clinical remission of the skin condition (Copeman, 1969). The subchondral collapse from gout may produce the 'arrowhead' deformities commonly seen in psoriasis. Bony ankylyosis may occur in both conditions. However, in psoriasis the
35
soft-tissue swelling is Symmetrical and associated with juxta-articular osteoporosis. The exclusion of gout in a patient with psoriasis may depend on biochemical confirmation. The possibility of gout in acute obstructive uropathy should be borne in mind. It has been suggested, although not proved, that acute renal failure might occasionally be produced by the deposition of uric acid crystals following the use of radiological contrast media when given in single large doses (Mudge, 1971; Postlethwaite and Kelley, 1971). It is not clear whether the acute deposition of uric acid is a response to the contrast medium or of the dehydration often employed prior to excretion urography. No example has been seen in the present series. The index of suspicion for the diagnosis of gout is generally low both clinically and radiologically, a point emphasised 27 years ago by McCracken et al. (1946). It is accepted that the radiological changes of gout occur late and are often nonspecific (Copeman, 1969), and Golden (1956) suggests that only one-third o f advanced cases show sufficient characteristic radiological evidence to allow a diagnosis to be made. However, the radiologist is in a position, not only to raise the possibility of the diagnosis, but to demonstrate its extent and severity. Special consideration should be given to patients with unusual osteophytosis or degenerative osteoarthrosis with 'cyst' formation, and to patients with diseases in which the incidence of secondary hyperuricaemia is high. REFERENCES BRAILSFORD, J. F. (1959), The radiology of gout. British Journal of Radiology, 32, 472-478. COP£MAN, W. S. C. 0969) (ed.). Textbookof Rheumatic Diseases, p. 456. Livingstone. CULLEN, W. (1778). First Lines in the Praetice of Physic,
2nd edn, Vol. 1. Creech, Edinburgh. DIxoN, A. ST. J. (•967). Personal communication quoted in Hughes et aL, 1968. DIXON,A. ST. J. (1972). Recent trends. Medicine, Section 1, p. 9. London Medical Education (International) Ltd. DODDS, W. J. & STEIN'BACH,[-I. L. (1966). Gout as associated with calcification of cartilage. New England Journal of Medicine, 275, 745-749.
EISEN, A. Z. & SEEGMILLER,J. E. (1961). Uric acid metabolism in psoriasis. Journal of Clinical Investigation, 40, 1486-1494. GARROD,A. B. (1848). Observations on certain pathological conditions of the blood and urine in gout, rheumatism and Bright's disease. Transactions of Medical and Chirurgical Society, ¥ol. 31, p. 85, GOLDEN, R. (1956). Diagnostic Roentgenology, Part 2, pp. 5550-5553. Williams and Wilkins, Baltimore. GOOD, A. E. & RAPP, R. (1967). Chondrocalcinosis of the
36
CLINICAL RADIOLOGY
knee with gout and rheumatoid arthritis. New England Journal of Medicine, 277, 286-290. GUTMAN, A. B. (1953). Primary and secondary gout. Annals of lnternal Medicine, 39, 1062-1076. HAJKOVA.,Z., STREDA, f . & SKRttA, F. (1965). Hyperostoti spondylosis and diabetes mellitus. Annals of Rheumatic Diseases, 24, 536-543. HALL, A. P_ (1965). Correlations among hyperuricemia, hypercholesterolemia, coronary disease and hypertension. Arthritis and Rheumatism, 8, 780~795. HUNCH, P. S. (1935). A clinic on some diseases of joints. Medical Clinics of North America, 19, 551-583. HUBER, (1896). The use of x-rays in internal medicine. Deutsche Mediziuische Wochenschrift, 22, 182195. HUGHES, G. R., BARNES, C. G. & MasoN, R. M. (1968). Bony ankylosis in gout. Annals of Rheumatic Diseases, 27, 67-70. HUNDER, G. G_, WORTHINGTON, J. W. & BICKEL, W. H. (1968). Avascular necrosis of the femoral head in a patient with gout. Journal of the American Medical Association, 203, 101-103. ISHMAEL, W. K. (1948). The familial aspects of gout, diabetes mellitus and obesity. Journal of the Oklahoma State Medical Association, 38, 415-423. JacoBs, P, (1973). Atlas of Hand Radiographs, p. 248. Harvey Miller and Medcalf, London. JAYSON, M. I. V. (1973). Personal communication. KITTREDOE, W. E. & DOWNS, R. (1952). The role of gout in the formation of urinary calculi. Journal of Urology, 67, 841-847. LAMBETH, J. T., BURNS-Cox, C. J. & MACLEANR. (1970). Sacroiliac gout associated with haemoglobin E and hypersplenism, Radiology, 95, 413M15. LICHTENSTEIN, L., SCOTT, H. W. & LEVIN, M. [-:[. (1956). Pathologic changes in gout: survey of 11 necropsied cases. American Journal of Pathology, 32, 871-895. LUDWIG, A. O., BENNETT, G. A. & BAUER, W. (1938). A rare manifestation of gout; widespread ankylosis simulating rheumatoid arthritis_ Annals of lnternal Medicine, 11, 1248-1276. MARTEL, W. (1968). The overhanging margin of bone; a roentgenologic manifestation of gout. Radiology, 91, 755-756. MARTEL, W., KOHLER, C- C., THOMSON, G. R. & CARTER, T. L. (1970). A roentgenologically distinctive arthropathy in some patients with the pseudogout syndrome. American Journal of RoentgenolOgy, 109, 587-607. McCLURE, C. W. & MCCARTY, E. D. (1919). Roentgenographic studies in gout. Archives of Internal Medicine, 24, 563-579. MCCRAC~N, J. P., OWEN, P. S. & PRATT, J. H. (1946), Gout; still a forgotten disease. Journal of the American Medical Association, 131, 367-372. MmDLEMrSS, J. H. & 'BRABAND, H. (1962). Juvenile gout. Clinical Radiology, 13, 149-152.
MUDGE, G. H, (1971). Uricosuric action of cholecystographic agents. A possible factor in nephrotoxicity, New England Journal of Medicine, 284, 929-933. PAGET, SIR J. (1882). Additional cases of osteitis deformans. Medico-Chirurgical Transactions, 65, 225-236. POSTLEXHWAITE,A. E. & KELLEY, W. N. (1971). Uricosuric effect of radio contrast agents. A study in man of four commonly used preparations. Annals of Internal Medicine, 74, 845-852. RADCLIFF, J. Quoted in STRUTHER,E. (1716). Dr Radchff's Practical Dispensary containing a Complete Body of Prescriptions Fitted for all Disease, Internal and External Digested under Proper Heads. Rivington, London. RAUsc~, W. M. (1950). Gout in a girl 3½ years old. Medizinische Monatsshrift (Stuttgart), 4, 931-933. SCHEELE, K. W. (1766). Chemical examination of urinary calculi_ Opuscula, 2, 73. SCHOEN, D_ (1970). Hyperostofic spondylosis and diabetes mellitus. Symposium Ossium, ed. Jelliffe, A. M. & Strickland, B., pp. 175-177, E. Livingstone, Edinburgh and London. SCHOPF, E_ M. YON (1930). Gout in a five-weeks-old infant_ Klinische ~Fochenschrift, 9, 2148-2151. SCHORR, S., FR,KNKEL, M. & ADLER, E. (1956). Right unilateral thoracic spondylosis. Journal of the Faculty of Radiologists, 8, 59-65. SCUI)AMORE,C, (1823), A Treatise on the Nature and Course of Gout, 4th edn. Mallett, London. SMITH, G. E. & JONES, F. W. (1910). The Archaeological Survey of Nubia. Report for the 1907-8, Vol. 2, pp. 44, 269. National Printing Department, Cairo. STAPLE, T. W. (1971). Gout. Principals of Diagnostic Radiology, ed. Petchen, E. J., Koehler, P. R. & Davis, D. O., pp. 150-151. McGraw-Hill. TaLbOT, J. H. (1949). Diversity of gouty arthritis and its complications. Annals of Internal Medicine, 31, 555-569. TALBOT, J. H. (1967). Gout, 3rd ed. Grune & Stratton, New York and London. TKACH, S. (1970). Gouty arthritis of the spine. Clinical Orthopaedics and Related Research, 71, 81-86. UNGERLE~DER, H. E. (1954). Internist and life insurance. Annals of Internal Medicine, 41, 124-130. WATTS, R. W, E. (1973). Gout. Medicine, Vol. 12, pp. 783-789. London Medical Education (International) Ltd. WEISSMAN, G. & RITa, G. A. (1972). Molecular basis of gouty inflammation: interaction o f monosodium urate crystals with lysosomes and liposomes. Nature (New Biology), 240, 167-172. WENZEL, C. (1824). Cited by Schmorl, G. & Junghanns, H. (1951). Die gesunde und Kranke Wirbelsdule in Rdntgenbild und Klinik, 2nd edn, p. 209. G. Thieme, Stuttgart_ WOLLASTON,W. H. (1797). Gouty and urinary concretions. Philosophical Transactions, 87, 386-391_ W~t~GHT, J. T. (1966). Unusual manifestations of gout. Australasian Radiology, 10, 365-374.
