Ann Rheum Dis (1983), 42, Supplement p 73

Radiology of the crystal-associated arthritideslAIN WATT

From the Department ofRadiology, Bristol Royal Infirmary, Bristol BS2 8HW

Introduction

Appreciation of the role and effects ofcrystals in arthropathy is advancingand changing rapidly. Threesubstances-namely, sodium biurate,calcium pyrophosphate dihydrate, andhydroxyapatite-are recognised tohave acute and/or chronic radiologicalarticular manifestations.

I will describe the pure radiologicalfeatures of each of these crystalassociated arthritides but it is essentialto appreciate that they may occur inany combination or they may coexistwith another arthropathy such asrheumatoid disease. The effect of eachon the other has not been fullyassessed, although a modifyinginfluence of pyrophosphate arthritison rheumatoid disease has been seen.'

Gout

The principal radiological features ofgout are due to the presence of tophi inor around bone. As chemotherapy isdesigned to prevent the formation ofsuch tophi many patients with gouthave either no abnormal appearancesat radiology or entirely non-specificfeatures. The individual radiologicalsigns of primary and secondary goutare identical, though in secondary goutan atypical joint may be primarilyaffected or established features ofbone erosion may be present inpatients seemingly sustaining theirfirst clinical attack.The initial radiological description

was made soon after the discovery ofx-rays' and has been followed by fullerdescriptions.3 In acute gout themetatarsophalangeal joint of the greattoe is affected in 80% of cases andill-defined soft tissue swelling may beappreciated, although less readily thanon clinical examination. Calcificationis absent and there are no features topermit a specific diagnosis.Osteoporosis may occur but is not

juxta-articular or periarticular indistribution as in rheumatoid disease,nor is it as extensive as that seen inregional migratory osteoporosis.

In chronic gout there ischaracteristically an asymmetricalpolyarticular arthropathy pre-dominantly affecting the meta-tarsophalangeal joints of the greattoe (Fig. 1). Overall, the distributionof joints affected is predominantlyperipheral, the feet, hands, wristsand elbows being the major sites.Sacroiliac, acromioclavicular andstemoclavicular joint disease are lesscommon. Distribution in the hands isthe inverse of that found inrheumatoid disease, with majorinvolvement of the terminal inter-phalangeal joints and least of themetacarpophalangeal joints. The soft

Fig. 2 Gross gout ofring finger. Noteextensive asymmetrical soft tissueswelling and well defined erosions. Anoverhanging margin sign is present(arrow).

Fig. 1 Tophaceous gout inmetatarsophalangeal joint ofgreat toe.

Note considerable soft tissue swellingand relative preservation ofjoint spacewidth. Well defined erosions are

present adjacent to joint. Bone densityis normal.

tissue abnormality is eccentric asym-metrical soft tissue swelling, presentonce tophaceous deposits haveexceeded about 5 mm. Soft tissuetophi are principally present aroundthe joints of the hands (Fig. 2), ankles,and elbows. Those at the elbow may bemistaken for rheumatoid nodules,while those at the tendoachilles inser-tion may mimic xanthomata. Soft tis-sue swelling about the dorsum of thefoot and os calcis is particularly charac-teristic. Calcification of purely soft tis-sue tophi is unusual and is thought toindicate either coexisting pyro-phosphate or hydroxyapatite deposi-tion, calcium dysmetabolism, or infec-tion. Ossification of tophi, thoughrare, has been reported on occasionsand typically is found in the hands.3The bony manifestations of urate

deposists are typical although notdiagnostic. Lesions in the soft tissues

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adjacent to bone induce areas ofpressure erosion with wasting orindentation of cortical outline creatingsharply defined sclerotic margins(Figs. 1, 2). There is no change inoverall bone density. Lesions in theperiosteum or cortex produceexpansile corticated, sharply defineddefects typically in a periarticularposition. The cortex is not usuallyintact over the lesion and thishook-like appearance, or overhangingmargin of Martel (Fig. 2), is a wellrecognised feature.4 Lesions within themedulla are typically round or oval inthe bony long axis with sharply definedsclerotic margins. Size normally variesfrom 1 to 3 mm, although frequentlyexceeds 5 mm. The sharply definednature of the bone erosion, with, at thisstage, the preservation of hyalinecartilage width, is in sharpcontradistinction to rheumatoiddisease. Indeed, despite substantialerosion cartilage width is preservedlate into the disease. Multiple

Fig. 3 Established joint disease withsubchondral collapse ofsubarticularcysts and secondary osteoarthritis atmetacarpophalangeal joints. Note newbone formation (arrows) not present inrheumatoid disease.

Fig. 4 Typical meniscalchondrocalcinosis. Note coarse

granular quality and absence ofany other abnormality.

Fig. 5 Gross capsular and ligamentous chondrocalcinosis at knee calcificationextends along poplitens bursa and into superior tibiofibular joint (arrows).

subarticular radiolucencies eventuallycoalesce and may be shownarthrographically to communicatewith the joint space like rheumatoidgeodes. Subsequent subchondralcollapse occurs with degenerativejoint disease (Fig. 3). Osteoporosisonly occurs as the result of disuse.Fibrous ankylosis is relativelycommon, whereas bony ankylosis isreported only occasionally,predominantly in the hands,particularly between carpal bones.Incidence of chondrocalcinosis is nohigher in those with gout than in acontrol population.Gout is also associated with bone

proliferation (Fig. 3) especially at theenthesis particularly with theformation of organised calcaneal spursand bridging syndesmophytes in the

thoracolumbar spine. It is not clear,however, whether this is amanifestation of gout or a reflection ofa broader dysmetabolism embracingobesity and diabetes mellitus. Uratecrystals in urine produce non-opaquecalculi with secondary obstructiveuropathy.The differential diagnosis of acute

gout includes either of the other twoacute crystal arthritides, septicarthritis and seronegativespondyloarthropathy. In establisheddisease the important differentialdiagnosis rests with psoriatic arthritis,because of the relative preservation ofbone density; the asymmetry oflesions; the presence of boneproliferation; and the predominantlyperipheral involvement, particularlythe terminal interphalangeal joints in

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Fig. 6 Pyrophosphate arthropathy. Gross new bone formation is mostpronounced at patellofemoral joint. There are apparent loose bodies insuprapatellar pouch.

the hands. Patchy sacroiliacinvolvement is reported in botharthritides. Inflammatory osteo-arthritis, particularly erosive osteo-arthritis, must also be considered as a

differential diagnosis. The preser-vation of the width of joint space in thepresence of well defined erosions ingout is seen also in multicentricreticulohystiocytosis and, in a singlejoint, of pigmented villonodularsynovitis.

Calcium pyrophosphate depositiondisease

Calcium pyrophosphate depositiondisease (CPPD) has been recognisedfor nearly 20 years but there is stillappreciable difficulty in itsterminology. Precise methods ofestablishing the diagnosis are beyond

the scope of this paper, but it isessential to specify three distinctfacets. Firstly, the presence ofcalcification radiographically-chondrocalcinosis; secondly, theoccurrence of acute clinical attacks orepisodes of arthritis-pseudogout;and, thirdly, the development of a des-tructive joint disease-pyrophosphatearthropathy. The principal radio-logical features of chondrocalcinosisand pyrophosphate arthropathy havebeen reviewed57 but the relationshipbetween them may prove difficult bothradiologically and clinically.

Radiologically, chondrocalcinosis isan age-related phenomenon with a

peak incidence of about 30% inelderly institutionalised patients.' Thepresence of chondrocalcinosis may notnecessarily indicate calciumpyrophosphate dihydrate as it may be

due to calcium phosphate dihydrate,hydroxyapatite, or, occasionally,brushite. When the features ofpyrophosphate arthropathy arepresent the correct specific diagnosismay be inferred, but if, for example,there has been total hyaline cartilageattrition chondrocalcinosis may not beseen.

CHONDROCALCINOSISThe detection of small quantities ofchondrocalcinosis requires ameticulous radiographic techniquewith optimal resolution.6 In mostcases, however, careful routineradiography will suffice. Radiologicalexamination of the knees (in theanteroposterior projection) gives a90% detection rate for chondro-calcinosis, 98% with antero-posterior views of the knees andhips, and 100% if the wrists are alsoexamined.7 Chondrocalcinosis mostcommonly occurs in fibrocartilage orhyaline cartilage, typically the menisciof the knee joint (Fig. 4), triangularligaments of the wrists, and theacetabular and glenoid labrae. Lessusually the annulus of theintervertebral discs and otherfibrocartilaginous structures areaffected. The calcification is typicallycoarse and granular in fibrocartilage,whereas in hyaline cartilage it isusually discrete, well defined, andlinear, paralleling the underlyingarticular bony cortex. Calcificationalso occurs in the synovium,particularly at the wrists, knees,metacarpophalangeal joints andmetatarsophalangeal joints and ischaracteristically ill defined and hazy.Gross calcification with jointdisruption may present a tophaceousappearance.' Calcification also occursin the joint capsule, particularlyaround the elbows, knees, (Fig. 5) andmetatarsophalangeal joints.Calcification at tendon insertion intobone, particularly the tendoachilles, iscommon and is typically linear andextensive compared with the morediscrete and focal involvement seen inhydroxyapatite deposition states.Occasionally calcification may occur inbursae when an ill-defined cloud-likequality may be observed.

PYROPHOSPHATE ARTHROPATHYThe structural joint changes ofpyrophosphate arthropathy most

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Fig. 7 Pyrophosphate arthropathy with very extensive joint disruption,resembling a charcot joint.

c lo s e I yresemble t h o s e o fosteoarthritis. There are, however,major differences. Pyrophosphatearthropathy affects more unusualsites, particularly the radiocarpal,metacarpophalangeal, trapezio-scaphoid, elbow, and the gleno-humeral joints. The distribution withinindividual joints is also different-forexample, the patellofemoral joint ofthe knee is predominantly affected(Fig. 6). Formation of new bone is vari-able and may be excessive with exuber-ant or massive osteophytes whencompared with osteoarthritis. Largemasses of trabeculated osteophytesdevelop (Fig. 6) and may appear sep-

arate from the underlying bone, sug-gesting loose bodies. Indeed, isolatedfragments of cartilage are also more

common, giving rise to genuine sepa-

rate intra-articular loose bodies.Unless they become substantial in size,however, these are distinguishedby the absence of bony trabeculaeon x-ray. Formation of osteophytevaries considerably; while in mostpatients considerable bone productionoccurs, in others it is virtuallyabsent with merely smooth ebur-nated articular surfaces. The extent ofthis subchondral sclerosis and theassociated subarticular radiolucenciesis far more pronounced in pyrophos-phate arthropathy than in osteo-arthritis. There is also a predilectionfor severe destructive changes in pyro-phosphate arthropathy and the like-ness of these joints to neuropathicjoints has been emphasised (Fig. 7).10Though this may be observed in thehip and knee joints, proximal row col-

lapse of the carpus associated withscapholunate diastasis is typical. Thesevere destructive nature of the arth-ropathy also produces severe facetdegenerative disease in the lum-bar spine, often with degenerativespondylolisthesis.Pyrophosphate arthropathy

predominantly affects large joints,particularly the knees, hips, andglenohumeral joints. Severe deformityof the knee joint may cause stressfractures of the upper tibia requiringjoint replacement. Indeed, carefulanalysis of most cases of deformingknee disease requiring total kneereplacement shows undoubtedfeatures of pyrophosphatearthropathy.

Clinical and radiological correlationis, however, fraught with difficulty.There is no definite relation betweenclinical arthritis and the presence ofchondrocalcinosis or pyrophosphatearthropathy. For example, extensiveradiographic abnormality may bepresent in entirely asymptomaticjoints. Furthermore, there is nodefinite relation between symptomsand the type of calcification present.Calcification may be ephemeral ornever seen although crystals may beclearly demonstrated from jointaspirate. There is no definiteprogression from chondrocalcinosis topyrophosphate arthropathy.

It is unclear whether pyrophosphatearthropathy and/or chondrocalcinosisare specifically related to anyparticular predisposing factor. Onlyprimary hyperparathyroidism andhaemochromatosis (both primary andsecondary) have such a proved causalrelationship."1 Indeed, apart from veryminor variations 'primary'pyrophosphate arthropathy oftencannot be distinguished on purelyradiological grounds from thatassociated with other diseases.' Subtledistinctions between primarypyrophosphate arthropathy andhaemochromatosis have beenemphasised in a meticulous study ofhand involvement (D Resnick, paperpresented at the International SkeletalSociety Meeting, San Francisco,1982). Joint space narrowing at thering and little finger metacarpo-phalangeal joints and crumbling ofarticular surfaces but with relative pre-servation of the radiocarpal joint andlarger hook-like osteophytes on the

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Fig. 8 Pyrophosphate arthropathy and rheumatoid disease. Note normal bonedensity, patchy involvement, and absence offresh erosion. Radiocarpal jointdisruption is consistent with either pyrophosphate arthropathy or old rheumatoiddisease with superadded degenerative disease.

metacarpal heads were found to bemore common in haemachromatosis.Scapholunate dissociation andchondrocalcinosis of the thumbcarpometacarpal joint were, how-ever, commoner in pyrophosphatearthropathy.

There is mounting evidence thatpyrophosphate arthropathy has a

modifying effect on other non-crystalarthritides and in a recent series ofpatients with chondrocalcinosispatients with rheumatoid proved byARA criteria had extremely modified

radiographic features.' This difficultyin distinguishing between rheumatoiddisease and pyrophosphatearthropathy has also been noted byothers.'2 In most patients withrheumatoid disease and pyro-phosphate arthropathy there are onlyoccasional erosions with the preserva-tion of normal bone density and anasymmetry of involvement (Fig. 8).The relationship between pyro-phosphate arthropathy and degenera-tive joint disease is ill understood, butit is clear that chondrocalcinosis occursmore often in previously traumatisedjoints as, for example, after meniscec-tomy," and that the degree of associ-ated pyrophosphate arthropathy inthese patients is worse in thosepatients who have evidence of osteo-arthritis elsewhere-for example, inthe terminal interphalangeal joints ofthe hands."3

Calcium hydroxyapatite depositiondisorders

EXTRA-ARTICU LARThe presence of foci of calcificationrelated to the shoulder joint is wellrecognised and although thesupraspinatus tendon (Fig. 9) is by farthe commonest affected numerousother foci are now acknowledged.These include the wrists (flexor carpiulnaris, less commonly flexor carpiradialis and extensor carpi ulnaris);adjacent to the metacarpophalangealjoints of the fingers and themetatarsophalangeal joints of the feet,especially the great toe (Fig. 10); theelbow, particularly the common flexorand extensor insertions; and at the hipjoint, particularly the glutealinsertions into the greater trochanter.Recently, involvement of the longuscolli with prepharyngeal soft tissueswelling has also been recognised. Thebursa may be affected on occasions,and this calcification may not be seenin radiographs.The condition is usually detected in

a single joint, but when multiple jointsare affected the onset is simultaneousin about one third and successive intwo thirds of cases. Typically, thepatient is aged between 40 and 70 andthe initial radiological features areill-defined soft tissue swelling adjacentto a joint, corresponding to the acuteinflammatory episode. Calcification isalmost always observed on the first

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Fig. 10 Acute hydroxyapatiteperiarthritis ofgreat toe. Noteill-defined soft tissue swelling anddiscrete, dense calcification adjacent tometatarsal head.

Fig. 9 Extensive hydroxyapatite periarthritis ofshoulder. There is amorphouscalcification extending from supraspinatus tendon into subdeltoid bursa and over

humeral head (arrows). Irregularity and sclerosis ofsupraspinatus insertion andfocal osteoporosis are present (open arrows).

examination and is initially ill definedand poorly localised. Thesupraspinatus is most common of therotator cuff tendons to be affected andis best seen on a film in externalrotation, whereas the infraspinatusand teres major may be seen on

intqrnal rotation posterior to thehumeral head and the subscapularisanterior. When calcification is illdefined symptoms can usually berelieved by aspiration underfluoroscopic control, with injection oflocal anaesthetic and steroid. With

time the calcification becomes more

localised, homogenous, and more

dense, with a linear or circularconfiguration. Around the shoulderthis may persist for many years and isresistant to needle aspiration. Asudden change in the clinical signs isoften associated with apparent ruptureand shedding of the calcificationeither into the shoulder joint or, morecommonly, into the adjacentsubdeltoid bursa from thesupraspinatus tendon. If there isextensive involvement of the tendon

rotator cuff instability may thendevelop, manifested by cephalicmigration of the humeral head withexcavation of the inferior aspect of theacromion. Though no abnormality ofbone is observed on initialpresentation with chronic diseasethere is usually bone resorption,sclerosis, and cyst formation atrotative cuff insertions.When multiple joints are involved

both shoulders usually demonstratethe abnormality. However, there isundoubtedly an incidence ofnon-symptomatic calcific disease.The calcification needs to be

distinguished from other causes of softtissue calcification in a periarticulardistribution, particularly thatassociated with calcium dysmeta-bolism (especially secondary hyper-parathyroidism and renalosteodystrophy) and in connective tis-sue disorders such as Ehlers-Danlossyndrome.

I NTRA -ARTICU LAR

Since Dieppe et al. found minutedense opacities within joints ofpatients with severe and destructivechanges,"4 hydroxyapatite has beenassociated with osteoarthritis,

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-qq.

Fig. 11 Advanced 'Milwaukee' shoulder. The acromium, coracoid process, andouter third of the clavicle are all destroyed. There is glenohumeral osteoarthritis.Calcification (arrow) is present in region offormer rotator cuff

particularly of the knee. It has alsobecome clear that calcification ofhyaline cartilage (chrondrocalcinosis)may also be due to hydroxyapatite"5and be associated with a pronouncedinflammatory arthropathy. Similarly, aprogressive and destructive arthritisoccurs at the shoulder joint,radiologically representing the severeend stage of rotator cuff instability(Fig. 1 1) (the 'Milwaukee shoulder').16In this condition there is considerablesynovial swelling with gross excavationand attrition of bone, particularly theacromium, the lateral end of theclavicle, the corocoid, and, latterly,the glenoid fossa. These appearances,when pronounced, are probablycharacteristic and entertain no seriousdifferential diagnosis; they are usuallybilaterally symmetrical. It is becomingclear that these patients also havedestructive arthritis of other joints,particularly the knee (Fig. 12), andthat hydroxyapatite deposition diseaseneeds to be considered in the presenceof severe Charcot-like knee andshoulder joints.

Hydroxyapatite deposition occursboth in joints and adjacent joints inmixed connective tissue disease and

scleroderma,17 though the relevance ofthis calcification in the pathogenesis ofboth arthritides is unclear. An erosivearthropathy with associatedcalcification should allow a specificdiagnosis of mixed connective tissuedisease rather than rheumatoid. In allof the hydroxyapatite depositiondiseases there is evidencescintigraphically of considerablemetabolic activity in the calcificationsite.

Conclusion

It is clear that the understanding of thecrystal-associated arthritides hasadvanced considerably in the pastdecade. Many radiological featuresthat would have been dismissed asdegenerative changes or osteoarthritisare now known to be manifestations ormodifications of osteoarthritis as aresult of the influence of crystaldeposition. Although the threeprincipal crystal arthritides may bedistinguished radiologically there is anappreciable overlap between them andthere are no exclusive pathognomonichallmarks to allow an absolutediagnosis.

Fig. 12 Left knee ofsame patient as Fig. 11. Extensive sclerosis and attrition ofbone in lateral compartment suggests an atypical osteoarthritis. There is possiblvchondrocalcinosis (arrow). Hydroxyapatite crystals were isolated from jointfluid.

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