485
WRIST ARTHROPATHY IN CALCIUM PYROPHOSPHATE DIHYDRATE DEPOSITION DISEASE PETER D. UTSINGER, DONALD RESNICK, and NATHAN J. ZVAIFLER Calcium pyrophosphate dihydrate deposition disease is associated with chondrocalcinosis and a characteristic radiographic abnormality. I n the wrist this abnormality consists of radiocarpal joint narrowing, sclerosis, and subchondral cystic degeneration of the carpal bones. These changes sometimes occur in the absence of chondrocalcinosis. T o investigate the significance of this occurrence, 18 patients with the radiographic abnormality of radiocarpal joint narrowing, sclerosis, and subchondral cystic degeneration were examined. Six had neither local wrist nor distant chondrocalcinosis. Five of the latter had wrist arthrocentesis and 4 had calcium pyrophosphate dihydrate crystals. Calcium pyrophosphate dihydrate deposition disease can occur in the absence of chon-
From the Departments of Medicine and Radiology, University Hospital of San Diego County and the Veterans Administration Hospital of San Diego, San Diego, California. Supported in part by Training Grant Ah1 05694. Peter D. Utsinger, M.D.: Formerly Fellow in Rheumatology, Department of Medicine, University of California, San Diego, currently Assistant Professor, Departmcnt of Medicine, University of North Carolina; Donald Resnick, M.D.: Assistant Professor of Radiology, Department of Radiology, University of California, San Diego, and San Diego Veterans Administration Hospital; Nathan J. Zvaifler, h1.D.: Professor of Medicine, Department of Medicine, University of California, San Diego. Address reprint requests to Nathan J. Zvaifler, M.D., University Hospital of San Diego County, 22.5 West Dickinson Street, San Diego, California 92102. Submitted for publication July 2, 1974; accepted October
7, 1974. Arthritis and Rheumatism, Vol. 18, No. 5 (September-October 1975)
drocalcinosis and the diagnosis is strongly suggested b y a characteristic radiographic picture.
Examination of synovial fluid by polarization microscopy has led to the recognition of the crystalinduced arthritides, gout, and calcium pyrophosphate tlihytlrate (CPPD) deposition disease. An additional clue suggesting the presence of CPPD is a characteristic radiographic finding, chondrocalcinosis, wliicli denotes the deposition of calcium-containing salts in liyaline or fibrocartilage. Chontlrocalcinosis is occasionally accompanied by distinctive radiographic abnormalities of the wrist, hantls, elbows, knees, and ankles consisting of joint space narrowing, eburnation, and subchondral lucencies (1). What has not been sufficiently recognized is that this radiographic pattern can occur in the absence of local or distant cartilage calcification (2). T h e purpose of this report is to describe 18 patients seen with this abnormal radiographic appearance in wrist x-rays, and to define their clinical disease.
MATERIALS AND METHODS Patients. Distiiicti\,e radiographic abnormalities of the wrist were seen in 23 patients iri\.estigatetl over a 1year period. TO be included i r i the 5tucly patielits had to sliow radiographic witleiice of wrist arthropathy consisting of radiocarpal joint space narrowing a n d sclerosis, a n d sub-
UTSINGER E T AL
486
Table 1. Clinical and RadiogrnPIlic Features
Patients 1 2 3 4 5 6 7 8 9 10 11
12 13 14 15 16
17 18
Age and Sex
Wrist .-2rthropathy*
73 M 57 M 41 M 83 M 58 M 51 M 66 M 79 M 83 M 73 M 78 M 51 M 77 M 85 M 95 F 78 M 75 M 80 F
+ + + + + + + + ++ + + + + + + + +
of I S
Prrlir?r/s ir>it/c II’list A r / / ~ r o / ~ n f / l y
Cliontlrocalcinosis Ij‘i-ist
Distant
0 0 0 0 0 0
0
+ -I+0 -I-
+0 + + 0 + +
0 0 0 0 0
0
++ +0 +-
+ + +
c.1) stals
IVrist Spnovitis*
Other Synovitis
+ + + +0
+ + + ++
MCP 0 0 0 0
CPPI)
0
0
0
+
-
+ 0
+
0 0
+ + + +0 0
0
+ 0 0 0
0 0 Knee 0 Knee
0 0 0 0 0 0 Knee Knee
*As defined in Materials and Methods.
+ = present; 0 = absent: - = not done. chondral cystic formations in the carpal bones. These patients were culled from the clinics and wards of the Sari Diego Veterans Administration Hospital and the IJniversity Hospital of San Diego. Five patients were eliminated from the study, 2 because of occupations that traumatized the wrists (auto mechanic and construction worker), a n d 1 patient because of a definable episode of severe wrist trauma. Another 2 patients were eliminated because of strongly positive serum rheumatoid factor tests although it was doubted that they had rheumatoid arthritis. 01 the remaining 18 patients, 11 were from the Veterans Hospital a n d 7 from the University Hospital. A careful joint examination was performed o n each patient. Synovitis was considered to be present if warmth and soft tissue swelling was palpated. Laboratory Procedures. T h e erythrocyte sedimentation rate (ESK) was performed by the Westergren method. Rheumatoid factor was measured by the bentonite flocculation test, and considered to be positive if present in a titer of 1/32 o r greater. Crystals were considered to be CPPD if they were triclinic and were shown to be weakly positive birefringent by compensated polarized microscopy. All crystals considered to be CPPI) appcared blue when their lorig axis was parallel to the direction of slow vibration of light, and yellow when at right angles. Determinations of phosphorous and uric acid were made by autoanalysis, calcium by atomic absorption, and alkaline phosphatase by an erizymatic rate reaction. Radiographic Investigations. A “joint survey” in 6 patients included radiographs of hands, wrists, elbows, shoulders, hips, symphysis pubis, knees, ankles, feet, and spine. A “chondrocalcinosis survey” including radiographs of hands, wrist, shoulders, symphysis pubis, hips, antl knees was made i n 4 patients. Eight others had less complete radiographic examination.
RESULTS T h e clinical and radiographic features of the 18 p t i e n t s are summarized in Table 1. N o patient h;id a significant family history of arthritis or an occupation requiring difficult manual labor. S o n e had a history of prolonged morning stiffness unresponsive to movement or heat, nor of psoriasis, urethritis, conjunctivitis, or inflammatory bowel disease. T h e most freq tieiit symptoms of wrist arthritis were pain, swelling, a n d stiffness. Pain and swelling were usually present for more than a year. T w o patients liad symptoms and electropliysiolob‘ TIC nieasiiremen ts consistent with carpal tunnel syndrome. ?’lie clinical course was analyzed according to the five patterns of CPPD disease essentially as described by hfcCarty (3). Type A (2 patients) was rliaracterized by intermittent, acute attacks of arthritis t h a t subsicled completely ( 1 patient) and a single attack of arthritis that subsidetl completely (1 patient). Type B (none) was repeated attacks of acute arthritis. Type C (8 patients) was progressive chronic arthritis with superimposed acute episodes. Type D (6 patients) was ;I progressive chronic artliritis without acute episodes. Type E (2 patients) was a n entirely asyniptomatic course. Both the acute and the chronic arthritis pretloni i iian tl y i nvolvetl the wrists and knees. Sixteen subjects were men and 2 were women. At the time of this study, their average age was 71 years, antl ranged from 41 to 95 years. Eight of the
487
WRIST ARTHROPATHY IN CPPD
Table 2. Comparison
of
Patients w i t h Wrist Arthropnthy
With Chondrocalcinosis Number Sex Age Pattern of arthritis Wrist synovitis
Fig 1. Patient 11: A wrist radiograph reveals radiocarpal joint space loss (‘\’), cyst \oritiatio~r (C), sclrr-osis (S), ~ n tl-irrnplar d {i 6rocctrt i loge ca Irificat ion ( C A L C).
10 patients who had a history of wrist pain or swelling had synovitis of the wrist. Two other patients Iiad wrist synovitis and no history of arthritis (Table 1). There was no evidence of tenosynovitis of finger extensors or the extensor carpi ulnaris. N o patient hat1 deviation of the wrists or fingers, or nodules, tophi, or inHanimation of the distal interplialangeal joints. T e n patients gave a history of knee pain or swelling; synovitis was noted unilaterally in 4 and a valgus rleformity in 1. Five patients liatl MCI’ or PIP pain or stiffness and synovitis was noted in 1. Four patients had elbow, ankle, or shoulder pain; 2 of these had no objective evidence of arthritis in these joints but 2 liad elbow Hexion contractures. During episodes of acute arthritis the erythrocyte sedimentation rate (ESK) was uniformally increased in all but 1 patient. Klieumatoid factors were nonreactive in 14, weakly reactive in 1 (1:16), and
12 10M,2F 76 C, D-75%
5
Without Chondrocalcinosis 6 6M 61 C, D-84% 5
not obtained in 3 patients. Urinalysis, blood glucose, calcium, phosphorus, and alkaline phosphatase were normal in the 15 subjects examined. These patients indicated neither historical nor physical evidence to suggest diabetes, hyperparathyroidism, hemochromatosis, or Wilson’s disease. Radiographic abnormalities i n the wrist included joint space loss, sclerosis, and cyst formation (Figures 1-3). T h e narrowing involved primarily the radiocarpal joint, particularly the radionavicular, and to a lesser extent the radiolunate spaces. A frequent finding was separation of the navicular and lunate bones, ie navicular-lunate “dissociation.” Sclerosis was most prominent in the radius and navicular bones. Subcliondral cysts were particularly common i n the proximal carpal row, and most characteristically involved the navicular and lunate bones. T h e cysts were marginal with a fine rim of sclerosis. Nine patients had chontlrocalcinosis in the wrist. Three others with no wrist chondrocalcinosis had chondrocalcinosis at other sites. I n the remaining 6 subjects, articular cartilage calcification was not identified in any joint examined radiographically. Other common radiographic findings were eburnation and cyst formation in the second and third metacarpoplialangeal joints and knees, narrowing and osteophyte formation in multiple joints, and periarticular ossicles at the proximal and distal interphalangeal joints (Figure 4). I n only 2 patients were small erosions noted, and these were at the proximal interphalangeal joints. Comparison of those patients with local or distant chondrocalcinosis ( 1 2 patients) with the group with no radiographic evidence of articular cartilage calcification at any site (6 patients) revealed only minor differences (Table 2 ) . In the group with chontlrocalcinosis there were 10 males and 2 females. T h e average age was 76 years. Nine patients described a chronic arthritis with or without acute attacks (Type C or D). One liad multiple acute attacks of arthritis with an asymptomatic intercritical period. One patient Iiad a single attack of arthritis and another was asymp
488
UTSINGER E T AL
Fig 2. Patient 12: Radiocarpal joint space narrowing ( N ) is associated w i t h eburnation and subchondral cyst formation ( C ) . Chondrocalcinosis ( C A W ) is present.
Fig 3. Patient 16: Severe radiocarpal joint space narrowing ( N ) and sclerosis are seen. Widening of the navicular-lunate space, navicular-lunate dissociation (D), is apparent. N o chondrocalcinosis is present.
489
WRIST ARTHROPATHY I N CPPD
were indistinguishable from those in the group without chondrocalcinosis, save for the presence of chondrocalcinosis. In particular, there was n o difference in any joint i n the distribution or degree of joint space narrowing, amount of sclerosis, or number, size, and location of cysts. T o define the latter group better, wrist arthrocentesis was performed in 5 patients. Each fluid was turbid and had many white blood cells. There was insufficient fluid for white blood cell counts i n all cases, but i n 2 the joint aspirate had greater than 16,000 cells/mm3. T h e finding that both intra- and extracellular crystals were compatible with CPPD i n 4 cases was surprising.
DISCUSSION
Fig 4. Patient 18: Cysts within the metacarpal heads (open arrows) are associated with second and third tnetacarpophalangeal joint space loss (closed arrows). Degenerative changes can be seen in the proximal and distal interphalangeal joints.
tomatic. Five patients had wrist synovitis of whom 1 also had Heberden’s nodes and a knee effusion, 1 Heberden’s nodes alone, and 1 a knee effusion. Of the remaining 7 patients, 1 had Heberden’s nodes and a knee effusion, 1 a knee effusion, and 1 Heberden’s nodes. T h e 6 patients without chondrocalcinosis were all males. Their average age was 61 years. Five had a chronic arthritis with or without acute attacks (Types C or D). One had a single episode of arthritis. Five patients had wrist synovitis; one of them had MCP synovitis and another Heberden’s nodes. T h e radiographic features of the group with chondrocalcinosis
T h e radiographic wrist abnormality in these patients resembles that described by Martel (1). T h e features of this distinctive degenerative disease are narrowing of the radiocarpal joint space with sclerosis, and subchondral carpal cysts. Similar changes may be noted in the metacarpophalangeal joints, elbows, ankles, and knees (4,5). T h e sparing of proximal interphalangeal joints, inferior radioulnar joint, and ulnar styloid is in striking contrast to the typical radiographic alterations of rheumatoid arthritis (6). This observation, plus the absence of prolonged morning stiffness, the limited amount of hypertrophied synovium, the absence of symmetricality, nodules, or deformities, and the negative rheumatoid factor, makes it unlikely that any of the group has rheumatoid arthritis. Trauma, occupational or accidental, can cause radiocarpal alterations (7,8). Fcr this reason patients with such a history were eliminated from the study. Osteoarthritis results in articular narrowing, sclerosis, and subchondral cyst formation. Individuals with “primary, generalized osteoarthri tis” bear similarities to the present patients. However, this disease predominantly affects women, predilects the interphalangeal joints, and spares the radiocarpal joints (9,lO). T h e inflammatory or erosive type of osteoarthritis is also most common in women, but the pattern of hand involvement differs somewhat from that of the primary form. There is a notable symmetry in DIP, PIP, and knee arthritis. Kadiographically, more than half the patients have marked erosive and proliferative changes of involved joints, but the radiocarpal joint is spared. I n Ehrlich’s series of inflammatory osteoarthritis, 157; of the patients subsequently
490
developed clinical features reminiscent of rheumatoid arthritis (11,12). This diagnosis is supported by the appearance of radiographic changes in many of them, including radionavicular joint space narrowing, and by the pathologic specimens and synovial fluid analyses i n some. O n the other hand, the absence of rheumatoid factors in 65% of these elderly patients suggests that a few may have had diseases mimicking rheumatoid arthritis, such as CPPD deposition disease. Six of the 18 patients had neither local nor distant chondrocalcinosis. Three of them had a complete joint survey, another a “chondrocalcinosis survey,” and 1 had radiographs of the wrists, hands, knees, elbows, and feet. I n the final patient radiographs were limited to the wrists and shoulders. Arthrocentesis disclosed calcium pyrophosphate crystals i n the wrists of 4 of these patients. T h e clinical, roentgenographic, and laboratory features attest to the similarity of the patients with and without chondrocalcinosis. I n this investigation crystallographic studies were not made. T h u s it is possible that the crystals observed were not CPPD crystals. However the criteria used were quite strict, requiring both triclinic form and weakly positive birefringence. T o the knowledge df the authors, none of the currently recognized phlogistic crystals in human articular tissues has similar morphologic or polariscopic characteristics. Although there is a paucity of information in the literature about CPPD crystal deposition disease without local or distant chondrocalcinosis, a number of authors have noted this association. McCarty (13), Moskowitz and Katz (14), Rubinstein and Shah (15), Smith and Phelps (16), and Pachas (17) have described similar patients. There are several explanations why chondrocalcinosis was not detected in some of the present patients with CPPD crystals. Perhaps the density of deposited calcium was not sufficient to be outlined by standard radiographic techniques. Industrial films are necessary to detect minute collections of calcium salts (18). This difficulty was recognized and therefore wellexposed and properly coned radiographs were obtained in every patient. Factors governing the localization of salt deposition are unknown. I t has been suggested that, if rapid precipitation occurs, superficial layers of cartilage are calcified, either alone or i n conjunction with intermediate layers. Superficial deposits could conceivably rupture leaving only minimal traces in the remaining intact cartilage. Martel has proposed that with progressive joint space narrowing, ie carti-
UTSINGER E T AL
lage destruction, calcified deposits may disappear (1). Most of the present patients had significant degenerative changes with joint space loss. However, two reasons make it unlikely that this mechanism was operative. First, a comparison of the degenerative changes in the group with wrist chondrocalcinosis and those without revealed no significant difference. T h e second is that the most likely localization for wrist calcification in CPPD deposition disease is in the triangular fibrocartilage at the ulnar side of the wrist (3). There were no degenerative changes in this compartment. Consequently the absence of calcification could not be ascribed to cartilage destruction. T w o groups of patients with similar clinical, roentgenographic, and laboratory abnormalities have been identified. T h e typical patient in both groups is a n elderly man with a history of chronic athritis involving primarily the wrists and the knees. Occasionally there are superimposed acute episodes of articular inflammation which are short-lived. Joint examination reveals no deformities, but synovitis of the wrist or knee is noted. Wrist radiographs show radionavicular joint space narrowing and sclerosis, and subchondral carpal cysts. Chondrocalcinosis may or may not be detected, but regardless of its presence CPPD crystals may be found on synovianalysis. It is concluded that CPPD deposition disease occurs commonly without chondrocalcinosis, and that certain clinical and radiographic features should strongly suggest the diagnosis.
ADDENDUM A complete description of the radiographic features found in this entity has been published in Radiology 113:633, 1974.
REFERENCES 1. Martel W, Champion E, Thompson G, et al: A roentgenologically distinctive arthropathy in some patients with pseudogout syndrome. Am J Roentgen01 109:587-605, 1970 2. Utsinger PD, Zvaifler NJ, Resnick D: Calcium pyrophosphate dihydrate deposition disease without chondrocalcinosis. (Submitted for publication) 3. McCarty DJ: Pseudogout (articular chondrocalcinosis), Arthritis and Allied Conditions. Eighth Edition. Edited by JL Hollander, DJ McCarty, Philadelphia, Lea & Febiger, 1972, pp 1140-1160 4. Martel W: Radiology of the rheumatic diseases. Arthri-
WRIST ARTHROPATHY IN CPPD
5.
6. 7.
8.
9.
10. 11. 12.
tis and Allied Conditions. Eighth Edition. Edited by JL Hollander, DJ McCarty. Philadelphia, Lea & Febiger, 1972, pp 82-136 Moskowitz R, Harris B, Schwartz A, et al: Chronic synovitis as a manifestation of calcium crystal deposition disease. Arthritis Rheum 14:109-116, 1971 Martel W: Pattern of rheumatoid arthritis in the hand and wrist. Radio1 Clin North Am 2:221-234, 1964 Schumacher H, Agudelo C, Labowitz R: Jackhammer arthropathy. JOCC Med 14:563-564, 1972 Kumulin T, Wiikeri M, Sumari P: Radiological changes in carpal and metacarpal bone phalanges caused by chain saw vibration. Br J Ind Med 30:71-73, 1973 Stecher RM: Heberden’s nodes. A clinical description of osteoarthritis of the finger joints. Ann Rheum Dis 14:l-10, 1955 Kellgren J: Primary generalized osteoarthritis. Bull Rheum Dis 4:4647, 1954 Ehrlich G: Inflammatory osteoarthritis. 1. T h e clinical syndrome. J Chronic Dis 25:317-328, 1972 Ehrlich G: Inflammatory osteoarthritis. 11. T h e super-
49 1
13.
14.
15. 16.
17.
18.
imposition of rheumatoid arthritis. J Chronic Dis 25: 635-643, 1972 McCarty DJ. Kohn NN, Faires JS: T h e significance of calcium phosphate crystals in the synovial fluid of arthritic patients: the “pseudogout syndrome.” I. Clinical aspects. Ann Intern Med 56:711-737, 1962 Moskowitz R, Katz D: Chondrocalcinosis and chondrocalsynovitis (pseudogout syndrome). Am J Med 43:322334, 1967 Rubinstein H, Shah D: Pseudogout. Semin Arthritis Rheum 2:259-280, 1972-1973 Smith J, Phelps P: Septic arthritis, gout, pseudogout and osteoarthritis in the knee of a patient with multiple myeloma. Arthritis Rheum 15:89-96, 1972 Pachas W: Pseudogout without chondrocalcinosis. A clinical, radiologic and pathologic study of 18 cases. Arthritis Rheum 15:121-122, 1972 (abstr) Parlee D, Freundlich I, McCarty DJ: A comparative study of roentgenographic techniques for detection of calcium pyrophosphate dihydrate deposits (pseudogout) in human cartilage. Am J Roentgen01 99:688-694, 1967
WRIST ARTHROPATHY IN CALCIUM PYROPHOSPHATE DIHYDRATE DEPOSITION DISEASE PETER D. UTSINGER, DONALD RESNICK, and NATHAN J. ZVAIFLER Calcium pyrophosphate dihydrate deposition disease is associated with chondrocalcinosis and a characteristic radiographic abnormality. I n the wrist this abnormality consists of radiocarpal joint narrowing, sclerosis, and subchondral cystic degeneration of the carpal bones. These changes sometimes occur in the absence of chondrocalcinosis. T o investigate the significance of this occurrence, 18 patients with the radiographic abnormality of radiocarpal joint narrowing, sclerosis, and subchondral cystic degeneration were examined. Six had neither local wrist nor distant chondrocalcinosis. Five of the latter had wrist arthrocentesis and 4 had calcium pyrophosphate dihydrate crystals. Calcium pyrophosphate dihydrate deposition disease can occur in the absence of chon-
From the Departments of Medicine and Radiology, University Hospital of San Diego County and the Veterans Administration Hospital of San Diego, San Diego, California. Supported in part by Training Grant Ah1 05694. Peter D. Utsinger, M.D.: Formerly Fellow in Rheumatology, Department of Medicine, University of California, San Diego, currently Assistant Professor, Departmcnt of Medicine, University of North Carolina; Donald Resnick, M.D.: Assistant Professor of Radiology, Department of Radiology, University of California, San Diego, and San Diego Veterans Administration Hospital; Nathan J. Zvaifler, h1.D.: Professor of Medicine, Department of Medicine, University of California, San Diego. Address reprint requests to Nathan J. Zvaifler, M.D., University Hospital of San Diego County, 22.5 West Dickinson Street, San Diego, California 92102. Submitted for publication July 2, 1974; accepted October
7, 1974. Arthritis and Rheumatism, Vol. 18, No. 5 (September-October 1975)
drocalcinosis and the diagnosis is strongly suggested b y a characteristic radiographic picture.
Examination of synovial fluid by polarization microscopy has led to the recognition of the crystalinduced arthritides, gout, and calcium pyrophosphate tlihytlrate (CPPD) deposition disease. An additional clue suggesting the presence of CPPD is a characteristic radiographic finding, chondrocalcinosis, wliicli denotes the deposition of calcium-containing salts in liyaline or fibrocartilage. Chontlrocalcinosis is occasionally accompanied by distinctive radiographic abnormalities of the wrist, hantls, elbows, knees, and ankles consisting of joint space narrowing, eburnation, and subchondral lucencies (1). What has not been sufficiently recognized is that this radiographic pattern can occur in the absence of local or distant cartilage calcification (2). T h e purpose of this report is to describe 18 patients seen with this abnormal radiographic appearance in wrist x-rays, and to define their clinical disease.
MATERIALS AND METHODS Patients. Distiiicti\,e radiographic abnormalities of the wrist were seen in 23 patients iri\.estigatetl over a 1year period. TO be included i r i the 5tucly patielits had to sliow radiographic witleiice of wrist arthropathy consisting of radiocarpal joint space narrowing a n d sclerosis, a n d sub-
UTSINGER E T AL
486
Table 1. Clinical and RadiogrnPIlic Features
Patients 1 2 3 4 5 6 7 8 9 10 11
12 13 14 15 16
17 18
Age and Sex
Wrist .-2rthropathy*
73 M 57 M 41 M 83 M 58 M 51 M 66 M 79 M 83 M 73 M 78 M 51 M 77 M 85 M 95 F 78 M 75 M 80 F
+ + + + + + + + ++ + + + + + + + +
of I S
Prrlir?r/s ir>it/c II’list A r / / ~ r o / ~ n f / l y
Cliontlrocalcinosis Ij‘i-ist
Distant
0 0 0 0 0 0
0
+ -I+0 -I-
+0 + + 0 + +
0 0 0 0 0
0
++ +0 +-
+ + +
c.1) stals
IVrist Spnovitis*
Other Synovitis
+ + + +0
+ + + ++
MCP 0 0 0 0
CPPI)
0
0
0
+
-
+ 0
+
0 0
+ + + +0 0
0
+ 0 0 0
0 0 Knee 0 Knee
0 0 0 0 0 0 Knee Knee
*As defined in Materials and Methods.
+ = present; 0 = absent: - = not done. chondral cystic formations in the carpal bones. These patients were culled from the clinics and wards of the Sari Diego Veterans Administration Hospital and the IJniversity Hospital of San Diego. Five patients were eliminated from the study, 2 because of occupations that traumatized the wrists (auto mechanic and construction worker), a n d 1 patient because of a definable episode of severe wrist trauma. Another 2 patients were eliminated because of strongly positive serum rheumatoid factor tests although it was doubted that they had rheumatoid arthritis. 01 the remaining 18 patients, 11 were from the Veterans Hospital a n d 7 from the University Hospital. A careful joint examination was performed o n each patient. Synovitis was considered to be present if warmth and soft tissue swelling was palpated. Laboratory Procedures. T h e erythrocyte sedimentation rate (ESK) was performed by the Westergren method. Rheumatoid factor was measured by the bentonite flocculation test, and considered to be positive if present in a titer of 1/32 o r greater. Crystals were considered to be CPPD if they were triclinic and were shown to be weakly positive birefringent by compensated polarized microscopy. All crystals considered to be CPPI) appcared blue when their lorig axis was parallel to the direction of slow vibration of light, and yellow when at right angles. Determinations of phosphorous and uric acid were made by autoanalysis, calcium by atomic absorption, and alkaline phosphatase by an erizymatic rate reaction. Radiographic Investigations. A “joint survey” in 6 patients included radiographs of hands, wrists, elbows, shoulders, hips, symphysis pubis, knees, ankles, feet, and spine. A “chondrocalcinosis survey” including radiographs of hands, wrist, shoulders, symphysis pubis, hips, antl knees was made i n 4 patients. Eight others had less complete radiographic examination.
RESULTS T h e clinical and radiographic features of the 18 p t i e n t s are summarized in Table 1. N o patient h;id a significant family history of arthritis or an occupation requiring difficult manual labor. S o n e had a history of prolonged morning stiffness unresponsive to movement or heat, nor of psoriasis, urethritis, conjunctivitis, or inflammatory bowel disease. T h e most freq tieiit symptoms of wrist arthritis were pain, swelling, a n d stiffness. Pain and swelling were usually present for more than a year. T w o patients liad symptoms and electropliysiolob‘ TIC nieasiiremen ts consistent with carpal tunnel syndrome. ?’lie clinical course was analyzed according to the five patterns of CPPD disease essentially as described by hfcCarty (3). Type A (2 patients) was rliaracterized by intermittent, acute attacks of arthritis t h a t subsicled completely ( 1 patient) and a single attack of arthritis that subsidetl completely (1 patient). Type B (none) was repeated attacks of acute arthritis. Type C (8 patients) was progressive chronic arthritis with superimposed acute episodes. Type D (6 patients) was ;I progressive chronic artliritis without acute episodes. Type E (2 patients) was a n entirely asyniptomatic course. Both the acute and the chronic arthritis pretloni i iian tl y i nvolvetl the wrists and knees. Sixteen subjects were men and 2 were women. At the time of this study, their average age was 71 years, antl ranged from 41 to 95 years. Eight of the
487
WRIST ARTHROPATHY IN CPPD
Table 2. Comparison
of
Patients w i t h Wrist Arthropnthy
With Chondrocalcinosis Number Sex Age Pattern of arthritis Wrist synovitis
Fig 1. Patient 11: A wrist radiograph reveals radiocarpal joint space loss (‘\’), cyst \oritiatio~r (C), sclrr-osis (S), ~ n tl-irrnplar d {i 6rocctrt i loge ca Irificat ion ( C A L C).
10 patients who had a history of wrist pain or swelling had synovitis of the wrist. Two other patients Iiad wrist synovitis and no history of arthritis (Table 1). There was no evidence of tenosynovitis of finger extensors or the extensor carpi ulnaris. N o patient hat1 deviation of the wrists or fingers, or nodules, tophi, or inHanimation of the distal interplialangeal joints. T e n patients gave a history of knee pain or swelling; synovitis was noted unilaterally in 4 and a valgus rleformity in 1. Five patients liatl MCI’ or PIP pain or stiffness and synovitis was noted in 1. Four patients had elbow, ankle, or shoulder pain; 2 of these had no objective evidence of arthritis in these joints but 2 liad elbow Hexion contractures. During episodes of acute arthritis the erythrocyte sedimentation rate (ESK) was uniformally increased in all but 1 patient. Klieumatoid factors were nonreactive in 14, weakly reactive in 1 (1:16), and
12 10M,2F 76 C, D-75%
5
Without Chondrocalcinosis 6 6M 61 C, D-84% 5
not obtained in 3 patients. Urinalysis, blood glucose, calcium, phosphorus, and alkaline phosphatase were normal in the 15 subjects examined. These patients indicated neither historical nor physical evidence to suggest diabetes, hyperparathyroidism, hemochromatosis, or Wilson’s disease. Radiographic abnormalities i n the wrist included joint space loss, sclerosis, and cyst formation (Figures 1-3). T h e narrowing involved primarily the radiocarpal joint, particularly the radionavicular, and to a lesser extent the radiolunate spaces. A frequent finding was separation of the navicular and lunate bones, ie navicular-lunate “dissociation.” Sclerosis was most prominent in the radius and navicular bones. Subcliondral cysts were particularly common i n the proximal carpal row, and most characteristically involved the navicular and lunate bones. T h e cysts were marginal with a fine rim of sclerosis. Nine patients had chontlrocalcinosis in the wrist. Three others with no wrist chondrocalcinosis had chondrocalcinosis at other sites. I n the remaining 6 subjects, articular cartilage calcification was not identified in any joint examined radiographically. Other common radiographic findings were eburnation and cyst formation in the second and third metacarpoplialangeal joints and knees, narrowing and osteophyte formation in multiple joints, and periarticular ossicles at the proximal and distal interphalangeal joints (Figure 4). I n only 2 patients were small erosions noted, and these were at the proximal interphalangeal joints. Comparison of those patients with local or distant chondrocalcinosis ( 1 2 patients) with the group with no radiographic evidence of articular cartilage calcification at any site (6 patients) revealed only minor differences (Table 2 ) . In the group with chontlrocalcinosis there were 10 males and 2 females. T h e average age was 76 years. Nine patients described a chronic arthritis with or without acute attacks (Type C or D). One liad multiple acute attacks of arthritis with an asymptomatic intercritical period. One patient Iiad a single attack of arthritis and another was asymp
488
UTSINGER E T AL
Fig 2. Patient 12: Radiocarpal joint space narrowing ( N ) is associated w i t h eburnation and subchondral cyst formation ( C ) . Chondrocalcinosis ( C A W ) is present.
Fig 3. Patient 16: Severe radiocarpal joint space narrowing ( N ) and sclerosis are seen. Widening of the navicular-lunate space, navicular-lunate dissociation (D), is apparent. N o chondrocalcinosis is present.
489
WRIST ARTHROPATHY I N CPPD
were indistinguishable from those in the group without chondrocalcinosis, save for the presence of chondrocalcinosis. In particular, there was n o difference in any joint i n the distribution or degree of joint space narrowing, amount of sclerosis, or number, size, and location of cysts. T o define the latter group better, wrist arthrocentesis was performed in 5 patients. Each fluid was turbid and had many white blood cells. There was insufficient fluid for white blood cell counts i n all cases, but i n 2 the joint aspirate had greater than 16,000 cells/mm3. T h e finding that both intra- and extracellular crystals were compatible with CPPD i n 4 cases was surprising.
DISCUSSION
Fig 4. Patient 18: Cysts within the metacarpal heads (open arrows) are associated with second and third tnetacarpophalangeal joint space loss (closed arrows). Degenerative changes can be seen in the proximal and distal interphalangeal joints.
tomatic. Five patients had wrist synovitis of whom 1 also had Heberden’s nodes and a knee effusion, 1 Heberden’s nodes alone, and 1 a knee effusion. Of the remaining 7 patients, 1 had Heberden’s nodes and a knee effusion, 1 a knee effusion, and 1 Heberden’s nodes. T h e 6 patients without chondrocalcinosis were all males. Their average age was 61 years. Five had a chronic arthritis with or without acute attacks (Types C or D). One had a single episode of arthritis. Five patients had wrist synovitis; one of them had MCP synovitis and another Heberden’s nodes. T h e radiographic features of the group with chondrocalcinosis
T h e radiographic wrist abnormality in these patients resembles that described by Martel (1). T h e features of this distinctive degenerative disease are narrowing of the radiocarpal joint space with sclerosis, and subchondral carpal cysts. Similar changes may be noted in the metacarpophalangeal joints, elbows, ankles, and knees (4,5). T h e sparing of proximal interphalangeal joints, inferior radioulnar joint, and ulnar styloid is in striking contrast to the typical radiographic alterations of rheumatoid arthritis (6). This observation, plus the absence of prolonged morning stiffness, the limited amount of hypertrophied synovium, the absence of symmetricality, nodules, or deformities, and the negative rheumatoid factor, makes it unlikely that any of the group has rheumatoid arthritis. Trauma, occupational or accidental, can cause radiocarpal alterations (7,8). Fcr this reason patients with such a history were eliminated from the study. Osteoarthritis results in articular narrowing, sclerosis, and subchondral cyst formation. Individuals with “primary, generalized osteoarthri tis” bear similarities to the present patients. However, this disease predominantly affects women, predilects the interphalangeal joints, and spares the radiocarpal joints (9,lO). T h e inflammatory or erosive type of osteoarthritis is also most common in women, but the pattern of hand involvement differs somewhat from that of the primary form. There is a notable symmetry in DIP, PIP, and knee arthritis. Kadiographically, more than half the patients have marked erosive and proliferative changes of involved joints, but the radiocarpal joint is spared. I n Ehrlich’s series of inflammatory osteoarthritis, 157; of the patients subsequently
490
developed clinical features reminiscent of rheumatoid arthritis (11,12). This diagnosis is supported by the appearance of radiographic changes in many of them, including radionavicular joint space narrowing, and by the pathologic specimens and synovial fluid analyses i n some. O n the other hand, the absence of rheumatoid factors in 65% of these elderly patients suggests that a few may have had diseases mimicking rheumatoid arthritis, such as CPPD deposition disease. Six of the 18 patients had neither local nor distant chondrocalcinosis. Three of them had a complete joint survey, another a “chondrocalcinosis survey,” and 1 had radiographs of the wrists, hands, knees, elbows, and feet. I n the final patient radiographs were limited to the wrists and shoulders. Arthrocentesis disclosed calcium pyrophosphate crystals i n the wrists of 4 of these patients. T h e clinical, roentgenographic, and laboratory features attest to the similarity of the patients with and without chondrocalcinosis. I n this investigation crystallographic studies were not made. T h u s it is possible that the crystals observed were not CPPD crystals. However the criteria used were quite strict, requiring both triclinic form and weakly positive birefringence. T o the knowledge df the authors, none of the currently recognized phlogistic crystals in human articular tissues has similar morphologic or polariscopic characteristics. Although there is a paucity of information in the literature about CPPD crystal deposition disease without local or distant chondrocalcinosis, a number of authors have noted this association. McCarty (13), Moskowitz and Katz (14), Rubinstein and Shah (15), Smith and Phelps (16), and Pachas (17) have described similar patients. There are several explanations why chondrocalcinosis was not detected in some of the present patients with CPPD crystals. Perhaps the density of deposited calcium was not sufficient to be outlined by standard radiographic techniques. Industrial films are necessary to detect minute collections of calcium salts (18). This difficulty was recognized and therefore wellexposed and properly coned radiographs were obtained in every patient. Factors governing the localization of salt deposition are unknown. I t has been suggested that, if rapid precipitation occurs, superficial layers of cartilage are calcified, either alone or i n conjunction with intermediate layers. Superficial deposits could conceivably rupture leaving only minimal traces in the remaining intact cartilage. Martel has proposed that with progressive joint space narrowing, ie carti-
UTSINGER E T AL
lage destruction, calcified deposits may disappear (1). Most of the present patients had significant degenerative changes with joint space loss. However, two reasons make it unlikely that this mechanism was operative. First, a comparison of the degenerative changes in the group with wrist chondrocalcinosis and those without revealed no significant difference. T h e second is that the most likely localization for wrist calcification in CPPD deposition disease is in the triangular fibrocartilage at the ulnar side of the wrist (3). There were no degenerative changes in this compartment. Consequently the absence of calcification could not be ascribed to cartilage destruction. T w o groups of patients with similar clinical, roentgenographic, and laboratory abnormalities have been identified. T h e typical patient in both groups is a n elderly man with a history of chronic athritis involving primarily the wrists and the knees. Occasionally there are superimposed acute episodes of articular inflammation which are short-lived. Joint examination reveals no deformities, but synovitis of the wrist or knee is noted. Wrist radiographs show radionavicular joint space narrowing and sclerosis, and subchondral carpal cysts. Chondrocalcinosis may or may not be detected, but regardless of its presence CPPD crystals may be found on synovianalysis. It is concluded that CPPD deposition disease occurs commonly without chondrocalcinosis, and that certain clinical and radiographic features should strongly suggest the diagnosis.
ADDENDUM A complete description of the radiographic features found in this entity has been published in Radiology 113:633, 1974.
REFERENCES 1. Martel W, Champion E, Thompson G, et al: A roentgenologically distinctive arthropathy in some patients with pseudogout syndrome. Am J Roentgen01 109:587-605, 1970 2. Utsinger PD, Zvaifler NJ, Resnick D: Calcium pyrophosphate dihydrate deposition disease without chondrocalcinosis. (Submitted for publication) 3. McCarty DJ: Pseudogout (articular chondrocalcinosis), Arthritis and Allied Conditions. Eighth Edition. Edited by JL Hollander, DJ McCarty, Philadelphia, Lea & Febiger, 1972, pp 1140-1160 4. Martel W: Radiology of the rheumatic diseases. Arthri-
WRIST ARTHROPATHY IN CPPD
5.
6. 7.
8.
9.
10. 11. 12.
tis and Allied Conditions. Eighth Edition. Edited by JL Hollander, DJ McCarty. Philadelphia, Lea & Febiger, 1972, pp 82-136 Moskowitz R, Harris B, Schwartz A, et al: Chronic synovitis as a manifestation of calcium crystal deposition disease. Arthritis Rheum 14:109-116, 1971 Martel W: Pattern of rheumatoid arthritis in the hand and wrist. Radio1 Clin North Am 2:221-234, 1964 Schumacher H, Agudelo C, Labowitz R: Jackhammer arthropathy. JOCC Med 14:563-564, 1972 Kumulin T, Wiikeri M, Sumari P: Radiological changes in carpal and metacarpal bone phalanges caused by chain saw vibration. Br J Ind Med 30:71-73, 1973 Stecher RM: Heberden’s nodes. A clinical description of osteoarthritis of the finger joints. Ann Rheum Dis 14:l-10, 1955 Kellgren J: Primary generalized osteoarthritis. Bull Rheum Dis 4:4647, 1954 Ehrlich G: Inflammatory osteoarthritis. 1. T h e clinical syndrome. J Chronic Dis 25:317-328, 1972 Ehrlich G: Inflammatory osteoarthritis. 11. T h e super-
49 1
13.
14.
15. 16.
17.
18.
imposition of rheumatoid arthritis. J Chronic Dis 25: 635-643, 1972 McCarty DJ. Kohn NN, Faires JS: T h e significance of calcium phosphate crystals in the synovial fluid of arthritic patients: the “pseudogout syndrome.” I. Clinical aspects. Ann Intern Med 56:711-737, 1962 Moskowitz R, Katz D: Chondrocalcinosis and chondrocalsynovitis (pseudogout syndrome). Am J Med 43:322334, 1967 Rubinstein H, Shah D: Pseudogout. Semin Arthritis Rheum 2:259-280, 1972-1973 Smith J, Phelps P: Septic arthritis, gout, pseudogout and osteoarthritis in the knee of a patient with multiple myeloma. Arthritis Rheum 15:89-96, 1972 Pachas W: Pseudogout without chondrocalcinosis. A clinical, radiologic and pathologic study of 18 cases. Arthritis Rheum 15:121-122, 1972 (abstr) Parlee D, Freundlich I, McCarty DJ: A comparative study of roentgenographic techniques for detection of calcium pyrophosphate dihydrate deposits (pseudogout) in human cartilage. Am J Roentgen01 99:688-694, 1967
