Temporomandibular joint involvement in generalized osteoarthritis and rheumatoid arthritis: a clinical, arthroscopic, histologic, and immunohistochemical study

Temporomandibular joint involvement in generalized osteoarthritis and rheumatoid arthritis: a clinical, arthroscopic, histologic, and immunohistochemical study

Int. J, Oral Maxillofac, Surg. 1997; 26." 10-16 Printed in Denmark. All rights reserved Copyright 9 Munksgaard 1997 [ntemationaUouma] of Oral & Maxi...

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Int. J, Oral Maxillofac, Surg. 1997; 26." 10-16 Printed in Denmark. All rights reserved

Copyright 9 Munksgaard 1997 [ntemationaUouma] of

Oral & MaxillofacialSurgery ISSN 0901-5027

Aesthetic and reconstructivesurgery

Temporomandibular joint involvement in generalized osteoarthritis and rheumatoid arthritis: a clinical, arthroscoplc, hlstologic, and immunohistochemical study

G6ran W. Gynther 1, Anders B. Holmlund 1, Finn P. Reinholt 2, Staffan Lindblad 3 1Department of Oral and Maxillofacial Surgery and 2Division of Pathology, Huddinge University Hospital, Karolinska Institute, Huddinge; aDepartment of Rheumatology, Karolinska Hospital, Karolinska Institute, Stockholm, Sweden

G. W. Gynther, A. B. Holmlund, F. P. Reinholt, S, Lindblad." Temporomandibular joint involvement in generalized osteoarthritis and rheumatoid arthritis." a clinical, arthroscopic, histologic, and immunohistoehemical study. Int. J. Oral Maxill@~c. Surg. 1997; 26: 10-16. 9 Munksgaard, q997 Abstract. Twenty patients having generalized osteoarthritis (GOA) and symptomatic temporomandibular joints (TMJs) were compared with 22 patients having rheumatoid arthritis (RA) and TMJ symptoms, and also with an agematched reference tissue material obtained at autopsy from 17 TMJs. Muscle tenderness was commoner in GOA. Arthroscopically, high frequencies of synovitis, degenerative changes, and fibrosis were observed in both groups, with more pronounced inflammatory and degenerative changes in RA patients, despite a shorter duration of TMJ symptoms. A correlation was noted between lateral joint tenderness and pronounced synovitis in RA patients. Histologic and immunohistochemical examinations added useful information to arthroscopy and showed similarly high frequencies of synovial inflammation in GOA and RA patients, differing clearly from those in the reference material. Connective-tissue degeneration was commoner in GOA patients. GOA and RA probably have different causes, but, interestingly, the tissue reaction was similar in the TMJs, although pronounced inflammatory and degenerative changes seemed to develop faster in RA.

Generalized osteoarthritis (GOA) is primarily a noninflammatory disease with involvement of three or more joints or groups of joints 33. The most commonly observed constellation of findings in GOA include involvement of the interphalangeal, first metatarsophalangeal, and first carpometacarpal joints, followed (in order of decreasing frequency) by the knees, cervical and lum-

bar spine, metacarpophalangeal joints, hips, and wrists 33. In localized osteoarthritis (which mainly affects the knees, hips, or hands), it has been suggested that the disease has a major inflammatory component 8"17'24'25'34, but the presence, extent, and character of the inflammatory changes in the synovial membrane remain controversial 6. Unlike localized

Key words: temporomandibular joint; generalized osteoarthritis; rheumatoid arthritis; clinical findings; arthroscopy; immunohistochemistry. Accepted for publication 3 July 1996

osteoarthritis, it has been proposed that GOA represents some still unknown genetic disorder in the structure, biochemistry, or metabolism of articular cartilage 26. For instance, a polymorphic genetic error in the gene for type II collagen may play a role 2~ Temporomandibular joint (TMJ) involvement in GOA has only been investigated radiographically 1~ In contrast,

T M J involvement in GOA and R A T M J involvement in r h e u m a t o i d arthritis (RA) has been extensively assessed clinically a n d radiographically230,22,31,36. Recently, a r t h r o s c o p i c a n d histologic findings have been rep o r t e d 436. N o i m m u n o h i s t o c h e m i c a l studies of the T M J have been p e r f o r m e d a p a r t from a study o n patients with i n t e r n a l d e r a n g e m e n t ax. However, the biopsies were o b t a i n e d from areas with "fibrillations" or adhesions, a p p a r e n t l y n o t f r o m sites with signs o f synovial int l a m m a t i o n . Therefore, the relevance o f these results must be questioned. In the present study, clinical, a r t h r o scopic, histologic, a n d i m m u n o h i s t o chemical changes in G O A patients with T M J involvement were investigated. T h e findings were c o m p a r e d with those in R A patients. Histologic a n d imm u n o h i s t o c h e m i c a l changes in b o t h G O A a n d R A patients were also comp a r e d with age-matched reference material o b t a i n e d at autopsy. E m p h a s i s was placed o n d e t e r m i n i n g w h e t h e r inf l a m m a t o r y changes are present in the symptomatic TMJ in G O A , a n d whether there are differences between T M J involvement in G O A a n d R A patients. The use o f diagnostic m a r k e r s in pathologic conditions" affecting the T M J together with i m m u n o h i s t o c h e m istry was also investigated. Material and methods Patients

The study included patients with GOA or RA, all referred by rheumatologists because of symptoms of TMJ involvement. The criteria for GOA were those described by I~YRON ~; ALTMAN33. For RA, the criteria proposed by the American Rheumatism Association were used 3. The inclusion criterion for TMJ involvement was joint pain provoked or aggravated by mandibular movement, combined with crepitation or intermittent or chronic locking. In patients with symptoms from both TMJs, only the joint with most symptoms was studied. Table 1 shows the two groups according to the number of patients, sex, left/right joint ratio, and mean age. Fourteen of the 22 patients with RA were seropositive for rheuma-

toid factor at the time of investigation. The mean durations of TMJ symptoms were 21 months (range 2 4 8 months) in the GOA group and 14 months (range 2-36 months) in the RA group. Three patients in the RA group had received a single intra-articular injection of a corticosteroid (triamcinolone acetonide 10 rag) in the TMJ preoperatively. In the GOA group, one patient had received a single steroid injection, one patient three injections, and one patient four injections. The interval between the last injection and arthroscopy was at least 2 months. Three patients in the RA group were taking systemic corticosteroids (510 rag/day). Four patients in the RA group were being treated with disease-modifying drugs (auranofine, 6 mg/day, or methotrexate, 7.5 mg/week) combined with nonsteroidal anti-inflammatory drugs (NSAIDs). Twelve RA patients and four GOA patients were on NSAIDs alone. Thus, three RA patients and 16 GOA patients had received no medication for their joint disease. Methods

The clinical examination was performed with established techniques TM, and based on the following parameters: 1) lateral and posterior joint tenderness on palpation 2) ipsilateral muscle tenderness on palpation (>one masticatory muscle) 3) TMJ clicking (reciprocal or other) 4) TMJ crepitation 5) reduced opening <40 mm (including vertical overbite) 6) reduced protrusion <7 ram. Muscle and joint tenderness were assessed by palpation. Joint noises were assessed by both stethoscope and palpation. Mandibular movements were measured to the nearest millimetre with a ruler. The clinical examination was performed immediately before arthroscopy by the surgeon performing the arthroscopy (G.W.G.). The arthroscopic examination, based on an established technique ~2, was performed under local anaesthesia in the superior compartment. About 4 ml of lidocaine-adrenaline (10 mg/ml) was used to block the auriculotemporal nerve posterior to the condylar neck and to infiltrate the subcutaneous tissue lateral to the joint. The superior compartment was distended with about 2 ml isotonic saline solution at room temperature. Puncture was performed by an inferolateral approach. An outflow was established, and

Table 1. Sex ratio, left/right joint ratio, and age" of patients with generalized osteoarthritis (GOA) and rheumatoid arthritis (RA) and in reference material obtained at autopsy (REF) GOA Patients/j oints Male/female Left/right joint Age (years) mean/range

20/20 4/16 10/10 53/30-76

RA 22/22 7/15 11/ 11 44/18-76

REF 9/17 5/4 9/8 43/24-64

11

the superior compartment was examined with a 2.4-mm rod-lens forward-oblique telescope 30~ (Karl Storz GmbH, Tuttlingen, Germany). During the arthroscopic examination, the superior compartment was continuously irrigated with isotonic saline solution at room temperature. First, the posterior disc attachment was inspected for signs of synovitis or fibrosis. The arthroscope was then moved anteriorly in order to visualize the medial capsule and finally the anterior recess. The arthroscope was then moved back posteriorly, and the rest of the superior compartment (eminence, glenoid fossa, articular disc) was inspected for signs of degenerative changes. On the basis of the results of previous studies 9,13A6, the following signs were selected for classification of the arthroscopic findings:

Synovitis: 0) normal: pale, almost translucent synovial lining with a fine network of anastomosing small blood vessels; 1) mild: a localized area with capillary hyperaemia; 2) moderate to pronounced: generalized changes with capillary hyperaemia and synovial hyperplasia Degenerative changes: 0) normal: smooth, glossy white to yellow surfaces of the disc and articular fibrocartilage; 1) mild: a localized area of superficial fibrillation in the articular fibrocartilage and disc; 2) moderate: deep fibrillation down to the bone; 3) pronounced: generalized changes with deep fibrillation in the articular fibrocartilage and disc, exposure of the subchondral bone (eburnation) and disc perforation Fibrosis." 0) normal: no evidence of fibrotic bands; 1) mild: a localized area with fibrotic bands; 2) moderate to pronounced: several areas of fibrotic bands. In all patients, one synovial biopsy was obtained with an oriented semiblind technique from the part of the posterior disc attachment showing the highest grade of synovitis. To ensure that the biopsy was properly performed, we subsequently checked the biopsy area. The technique has been described in a recent study 9 and shown to be accurate 5. The specimens were immediately immersed in 4% neutral-buffered formaldehyde. They were then embedded in paraffin, and 3/~m-thick sections were cut and stained with haematoxylin-eosin and three different monoclonal antibodies against human epitopes: 1) DAKO monoclonal mouse antiproliferating cell nuclear antigen (PCNA); clone: PC10 (DAKO-PCNA, PC10) 2) DAKO monoclonal mouse anti-human T Cell, CD45RO; clone: UCHL1 (DAKOCD45RO, UCHL1) 3) DAKO monoclonal mouse antihuman macrophage, CD68; clone: KPI (DAKOCD68, KP1). For all three monoclonal antibodies, the avidin-biotin complex (ABC) method was used for staining.

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Gynther et aL

Fig. 1. Example of immunohistochemical staining with PCNA (proliferating cells) in RA patients with TMJ involvement showing grade 2, moderate changes with several foci of stained proliferated cells (arrows). Thd histologic classification of synovial inflammation in haemotoxytin-eosin stained sections was based on the results of an earlier study9, where variables such as synoviallining proliferation, location of inflammatory infiltrate, and the amount of small vascular profiles (overall estimate of number and size of arterial cross sections per tissue section) were investigated. Synovial inflammation was graded as: 0) normal: no inflammatory cells or increased amounts of vascular profiles, and a single layer of flat synoviocytes; 1) mild: increased amounts of vascular profiles and minor lymphocytic perivascular infiltrates or slight synovial lining proliferation; 2) moderate: increased amounts of vascular profiles, a diffuse inflammatory cell infiltrate, and synovial lining proliferation. Degeneration of the subsynovial connective tissue was evaluated as: 0) normal: none; 1) mild: localized areas with myxoid matrix; 2) moderate: several or large areas with myxoid matrix. The immunohistochemical stainings of the specimens were graded as: 0) normal: no stained cells; 1) mild: focal occurrence of stained cells; 2) moderate: several foci/large numbers of stained cells. An example is given in Fig. 1. In both groups, one biopsy had to be excluded because of inadequate biopsy material for routine histologic and immunohistochemical classifications. In the RA group, two additional biopsies were excluded from the immunohistochemical classification because of insufficient material. Microscopic examination was performed by two of the authors together (G.W.G. and ERR.) on coded sections without knowledge of the results of the arthroscopic examination. Reference material

The reference material, described in a previous study9, comprised 17 TMJs from nine

persons. Table 1 shows the sex, left/right joint ratio, and mean age. The following criteria were used for selection: first, no evidence in the patient's records of joint disease or TMJ arthropathy; second, no TMJ clicking or crepitus when the mandible was moved postmortem; and, finally, no macroscopic signs of degenerative or inflammatory joint disease a t dissection. The specimen included the posterior half of the disc and the anterior half of the posterior disc attachment. The histologic examination followed the procedure described for the patients. The statistical analysis was performed with the Spearman correlation coefficient, the Mann-Whitney U and Wilcoxon rank sum W test, and the exact logistic regression test 27.

Results Patients with GOA

The clinical and" arthroscopic findings of the 20 G O A patients are shown in

Tables 2 and 3. The histologic and immunohistochemical findings are illustrated in Fig. 2 and 3. N o significant correlation between the clinical features and any of the arthroscopic findings was observed. Degenerative changes were seen on arthroscopy in 19 joints, fibrosis in 18 joints, and synovitis in 14 joints. The nine patients with pronounced degenerative changes on arthroscopy frequently had pronounced fibrosis (0.01 < P--0.05). These patients were older (mean age 62 years) than the rest of the G O A patients (mean age 45 years) (0.01
Patients with RA

The clinical and arthroscopic findings of fhe 22 R A patients are shown in Tables 2 and 3. The histologic and im-

Table 2. Frequencies of clinical signs and symptoms in patients with generalized osteoarthritis (GOA) and rheumatoid arthritis (RA) No. GOA(n=20) Lateral joint tenderness Lateral and posterior joint tenderness Muscle tenderness Clicking Crepitation Reduced opening (<40 mm) mean (range) in mm Reduced protrusion (<7 mm) mean (range) in mm

10 6 8 10 13 13 38 (25-50) 8 7 (3-11)

RA(n=22) 11 2 2 9 14 16 37 (25-50) 13 6 (2-11)

T M J involvement in GOA and RA Table 3. Frequencies of arthroscopic diagnoses in patients with generalized osteoarthritis (GOA) and rheumatoid arthritis (RA) No.

GOA (n=20) Synovitis Grade 0=normal 1=mild 2=moderate to pronounced

RA (n=22)

6 7 7 '

6 4 12

Degenerative changes Grade 0=normal 1=mild 2=moderate 3=pronounced

1 10 0 9

0 6 8 8

Fibrosis Grade 0=normal 1=mild 2=moderate to pronounced

2 13 5

1 13 8

SYNOVIAL

INFLAMMATION

DEGENERATION

20"1

-NEGATWE

|

MiLD MODERATE

~OA - 19 JOINTS IA = 2 1 JOINTS ~EF - 11 JOI,'CI'S

GOA

~

R~F

OOA

RA

positive for PCNA. All three specimens without synovial inflammation on histologic examination showed a positive stain (mild) with one or more immunohistochemical markers (one specimen with CD45RO and with PCNA, one specimen with CD45RO, one specimen with CD68). Reference material

(in five specimens: three mild, two moderate) or were positive for immunohistochemical markers (CD45RO in five specimens: four mild, one moderate; PCNA in three specimens: one mild, two moderate; CD68 in two specimens: one mild, one moderate). Patients with moderate synovial inflammation on histologic examination had a shorter duration of TMJ symptoms than the rest of the group (0.001
munohistochemical findings are illustrated in Fig. 2 and 3. Joints that were tender on palpation showed a correlation with the presence of pronounced synovitis on arthroscopy (0.01
13

~EF

Fig. 2. Frequencies of histologic patterns (synovial inflammation and degeneration of subsynovial connective tissue) in patients with generalized osteoarthritis (GOA) and rheumatoid arthritis (RA) and in reference material (REF).

The hist0logic and immunohistochemical findings in the reference material are shown in Fig. 2 and 3. A complete synovial lining was seen on microscopic examination in all 17 specimens. On histologic examination, mild synovial inflammation and mild degeneration were present in three specimens each. Immunohistochemical stairiing with CD45RO was positive (mild) in six specimens. Among these were the three specimens with synovial inflammation on histologic examination. PCNA and CD68 were negative in all 17 specimens. Comparison between groups

The clinical sign that differed most between the GOA and R A groups was muscle tenderness, which was commoner in GOA patients (0.01<

P_<0.05).

Compared to GOA patients, R A patients more frequently displayed pronounced synovitis and moderate or pronounced degenerative changes on arthroscopy. Seven joints in the GOA group showed pronounced synovitis, compared to 12 joints in the R A group. Moderate or pronounced degenerative changes were observed in 16 joints, compared to nine joints in G O A patients. However, these differences were not significant. In the reference material, pathologic changes were infrequent, and the results differed clearly from those in the G O A and R A groups (P--<0.001), with the exception of myxoid degeneration. The histologic parameter that differed most between the GOA and R A groups was degeneration, which was commoner among GOA p a t i e n t s (0.01
14

Gynther et al. PCNA

~D4~RO

CD68 9

NEGATIVE

[] SULD

BI MODEILA"I~

GOA - 19 JOINTS

lo

lo-

0

0

GOA

RA

REF

R A . 19 JOINTS REF - I 7 JOINTS

I ,o

0'

GOA

RA

REF

GOA

RA

REF

Fig. 3. Frequencies of immunohistochemical patterns (PCNA showing proliferating cells, CD45RO showing T ceils, CD68 showing macrophages) in patients with generalized osteoarthritis (GOA) and rheumatoid arthritis (RA) and in reference material (REF).

Discussion

TMJ arthroscopy has demonstrated a high diagnostic accuracy for synovitis and degenerative changes of the cartilage and disc s'9'13 15,28. In those studies, as in this one, arthroscopy was performed only in the superior compartment,of the TMJ. Puncture of the inferior compartment, and particularly of the articulating anterior part, entails a considerable risk of damaging joint structures 12, and was therefore avoided. However, iiaflammation and degenerative changes in the inferior compartment are usually reflected in the superior compartment 32. Compared to previous studies by HOLMLUND et al. 16 and TEGELBERG & KOPP36, the frequency of clicking was clearly higher in the R A patients in the present study. An explanation may be that clicking other than reciprocal was also recorded in our study, whereas HOI~YmVND et al. and TEGELBERG ~; KOPI" only included reciprocal clicking. HOLMLUNDet a1.14 and MURAKAMIet al. 29 observed a weak correlation between lateral joint tenderness and pronounced synovitis in patients with internal derangement of the TMJ. In the present study, such a correlation was noted for R A patients, but not for GOA patients. The only clinical symptom that differed between R A and G O A patients was muscle tenderness, which was more frequent in the GOA patients. This,low frequency in R A patients contrasts with previous studies 16,36. This can perhaps be ascribed to the analgesic medication taken by the R A patients. In the present study, NSAIDs and/or systemic treatment with corticosteroids or diseasemodifying drugs were taken by far more R A patients than GOA patients. However, no relation between clinical symp-

toms and the presence or absence of analgesic medication was noted in this study. Reduced m a x i m a l mouth-opening has been observed in several studies of R A patients 16'22'36, in agreement with our results. LARHEIM et al. 22 and STmENGA et al. 35 concluded that maximal mouth-opening is not a reliable parameter for assessing TMJ function, since the active range of motion may be restricted for several reasons. Lal~I-~i~ et al. 22 noted that, although mouthopening was minimally impaired in RA patients, condylar translation was significantly restricted in many of the patients. It was therefore assumed that impaired TMJ mobility in patients with R A may result from fibrous bands in the joint and atrophy of the muscles. M t r R a ~ I et al. 3~ also suggested that intra-articular fibrous bands caused limited mouth-opening in patients with chronic locking of the TMJ. A previous arthroscopic study 16 showed a high frequency of fibrosis in R A patients, and the frequencies in our study were even higher for both R A and GOA patients. Surprisingly, no association with either reduced maximal opening or reduced protrusion was observed to support MURA~MI et al.'s assumption. However, most of the fibrotic bands observed were only single bands with probably little clinical importance. The frequency of synovitis on arthroscopy was high in GOA patients, in agreement with previous studies of osteoarthritis in the hand, knee, and hip joints 8,17'24'34. Compared to the GOA patients, there was a tendency to more pronounced synovitis in the R A patients, despite a shorter duration of TMJ symptoms. This finding may indicate a more aggressive and faster development of the disease in RA, which has been substantiated by the observations

of erosions in a previous radiographic study l~ Surprisingly, several patients (six of 20 with GOA, six of 22 with RA) showed no arthroscopic signs of synovitis. However, all joints without synovitis showed either fibrosis (a sign of previous inflammation) or degenerative changes in the articular fibrocartilage and disc. On the basis of recent studies I~ we have classified the histologic and immunohistochemical findings as normal, mild, and moderate. The grade "pronounced" was consciously avoided because even in TMJs with pronounced changes on arthroscopy, the histologic findings often are moderate. On histologic examination, synovial inflammation was noted in most of the specimens with GOA and RA, and was microscopically indistinguishable between the groups, in agreement with other studies of knee joints 23,24. Almost all joints without arthroscopic signs of synovitis showed histologic or immunohistochemical signs of synovial inflammation. The frequencies were clearly higher than those reported for internal derangement of the TMJ 5,9. This finding seems appropriate since GOA and R A are diseases with a more pronounced effect on the joint tissues. The role of the synovial membrane in R A is not fully understood 7:sA9, but the occurrence of proliferating synovial lining cells has been regarded as an important sign of RA. In the R A patients in this study, all the specimens with synovial lining proliferation on histologic examination stained for PCNA. Several of the specimens without proliferation of synovial lining cells on histology also revealed synovial lining proliferation by PCNA, indicating that immnnohistochemical examination may improve the accuracy of diagnosing conditions affecting the TMJ. Interestingly, the fre-

T M J involvement in GOA and R A quency of synovial lining proliferation on histologic and immunohistochemical examinations was as high in G O A patients as in R A patients. This supports the view of similar tissue reactions in G O A and R A patients, as suggested for osteoarthritis in the knee and hip joints 6,8,17,24'34. Thus, it seems that injuries with different causes may evoke the same type of tissue response in TMJs. Alternatively, the results may indicate that G O A and R A have similar causes and/or pathogenesis. In conclusion, the present study showed similar frequencies of clinical signs and symptoms in the T M J , except for muscle tenderness, which was commoner in G O A patients. Arthroscopy revealed high frequencies of synovitis, fibrosis, and degenerative changes in the articular fibrocartilage and disc in both G O A and RA. However, the changes were more pronounced in the R A patients, despite a shorter duration of T M J symptoms. This indicates that R A patients may develop pronounced inflammation and degenerative changes in the T M J faster than G O A patients do. Similarly high frequencies of synovial inflammation, including synovial lining proliferation, were observed on histologic examination in both G O A and R A patients. This suggests similar tissue reactions in G O A and R A patients. Histologic and immunohistochemical findings in G O A and R A differed clearly (with the exception of degeneration of connective tissue in R A patients) from those in a n o r m a l reference material obtained at autopsy. Histology and immunohistochemistry added useful information to the arthroscopic examination, particularly in patients without arthroscopic signs of synovitis. Acknowledgments. This study was supported by grants from the Ulla and Gustaf af Uggla Foundation, the Swedish Association against Rheumatism, the Swedish Dental Society, the DPNOVA AB Foundation, the Swedish Medical Research Council, the King Gustaf V 80 years Anniversary Foundation, and the Karolinska Institute, Faculty of Dentistry. The authors are indebted to Inger Buskas and Anita Lindstr6m in the Division of Pathology for skilful preparation of histologic and immunohistochemical specimens.

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Address:

GOran W. Gynther, DDS, PhD Department of Oraland Maxillofacial Surgery Huddinge University Hospital Karolinska Institute S-141 86 Huddinge Sweden