Rheumatology 2004;43:1546–1554
Advance Access publication 1 September 2004
doi:10.1093/rheumatology/keh381
Muscle involvement in juvenile idiopathic arthritis
H. Lindehammar and B. Lindvall1
Objective. An observational study of changes in muscle structure and the relation to muscle strength in juvenile idiopathic
arthritis (JIA).
Methods. Fifteen children and teenagers (eight girls and seven boys) with JIA, aged 9–19 yr (mean age 16.1), were studied.
Muscle biopsies were obtained from the anterior tibial muscle and were examined using histopathological and immunohistochemical methods. Muscle fibre types were classified and fibre areas measured. As markers of inflammation, the major
histocompatibility complex (MHC) class I and class II and the membrane attack complex (MAC) were analysed. Results were
compared with biopsies from the gastrocnemius muscle in 33 young (19–23 yr) healthy controls. Isometric and isokinetic muscle
strengths were measured in ankle dorsiflexion. Strength was compared with reference values for healthy age-matched controls.
Nerve conduction velocities were recorded in the peroneal and sural nerves.
Results. Four of the 15 muscle biopsies were morphologically normal. Eleven biopsies showed minor unspecific changes. Two of
these also showed minor signs of inflammation. MHC class II expression was found in 4/15 patients, which was significantly
more than in the healthy controls (P ¼ 0.0143). The expression of MHC class I and MAC did not differ from that in the
controls. The mean area of type I fibres was lower than that of type IIA fibres in 12/13 biopsies. Muscle strength was
significantly reduced in the patient group. There was a significant positive correlation between muscle fibre area and muscle
strength. Nerve conduction studies were normal in all cases.
Conclusions. Changes in leg muscle biopsies appear to be common in children and teenagers with JIA. The presence of
inflammatory cells in the muscle and expression of MHC class II on muscle fibres may be a sign of inflammatory myopathy.
There are no findings of type II muscle fibre hypotrophy or neuropathy, as in adults with RA.
KEY WORDS: Muscle, Strength, Muscle fibre, Biopsy, Juvenile idiopathic arthritis, Juvenile chronic arthritis, Juvenile rheumatoid
arthritis, Nerve, Myositis.
In adult rheumatoid arthritis (RA), neuromuscular complications
such as neuropathy and myopathy are not uncommon [1]. Despite
the absence of any overt neuromuscular disease, muscle weakness
and hypotrophy may develop in some patients. Inactivity due to
the disease can result in a generalized reduction in muscle volume
and strength. Localized hypotrophy and weakness are sometimes
apparent in muscles close to active synovitis, especially in the thigh
muscle in knee arthritis [2–4]. This may be caused by disuse
hypotrophy or reflex inhibition elicited by pain or effusion in
the joint near to the weakened muscle [5, 6]. In one study of the
relationship between muscle weakness and muscle wasting in RA,
it was found that the weakness was more marked than the muscle
hypotrophy [7]. This could be the effect of arthrogenous muscle
inhibition or muscle dysfunction. Polymyositis and dermatomyositis occur in adults with RA. Muscle biopsies have shown
inflammation and signs of muscle fibre degeneration [8–11].
Myopathy may also be a complication of treatment with steroids
or antirheumatic drugs (chloroquine, D-penicillamine) [9, 12].
Vasculitic neuropathy, distal symmetrical neuropathy and
compression neuropathies are also seen in chronic RA [13–17].
Muscle fibres have different structural and functional features.
In normal human muscles they can be divided into three fibre
types: I, IIA and IIB. Type I is slow-twitch, oxidative. Type IIA
is fast-twitch, fatigue-resistant, oxidative/glycolytic. Type IIB is
fast-twitch, fatigue sensitive, glycolytic. Usually these types occur
in approximately equal proportions, but this may vary in different
muscles. Sometimes immature muscle fibres, type IIC fibres, are
seen in biopsies. The degree of physical activity influences the
structure of the muscles. Immobilization results in reductions in
muscle strength, muscle volume and muscle fibre area [18]. The
relative frequencies of the different fibre types may also change
in response to physical activity. In walking adults with chronic
hemiplegia, the proportion of type II fibres was increased in the
anterior tibial muscle of the weakened leg compared with the
healthy leg [19]. This was probably caused by a transformation of
type I muscle fibres to type II in response to different demands on
the muscle. Exercise influences both muscle fibre composition and
area. Muscle fibre areas, especially type II fibres, increase after
exercise, but the responses are variable among different muscles
and also depend on the type of exercise.
In children, muscle volume increases during growth. This occurs
by an increase in muscle fibre area; the number of muscle fibres
does not increase. During child growth the proportion of type I
fibres decreases and the proportion of type II fibres increases by
transformation of type I fibres to type II fibres [20]. In healthy
young people (16–27 yr of age) there were small changes in fibre
type frequencies but no significant differences in muscle fibre area
attributable to age [21]. Males usually have larger fibre areas than
females. In healthy adults, type II fibres have slightly larger areas
than type I fibres, especially in men [19, 21, 22]. In studies of adult
RA, hypotrophy of muscle fibres, predominantly type II fibres, has
been found [8–10, 23]. This seems to be more pronounced in
Department of Neuroscience and Locomotion, Division of Clinical Neurophysiology and 1Neuromuscular Unit, Department of Neuroscience and
Locomotion, Division of Neurology, Faculty of Health Sciences, Linköping University, Sweden.
Submitted 5 February 2004; revised version accepted 23 July 2004.
Correspondence to: H. Lindehammar, Department of Clinical Neurophysiology, University Hospital, SE- 581 85 Linköping, Sweden. E-mail:
[email protected]
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Rheumatology Vol. 43 No. 12 ß British Society for Rheumatology 2004; all rights reserved
Muscle involvement in JIA
patients treated with steroids. It is difficult to know whether this
is caused by the medicine or whether patients treated with steroids
often have a more severe disease [12].
The expressions of major histocompatibility complex (MHC)
class I and class II and membrane attack complex (MAC) in muscle
tissue are used as markers of inflammation [24]. MHC class I
molecules are normally expressed on nucleated cells, including
endothelial cells, but not or only very weakly on muscle cells. MHC
class II molecules are normally not or only weakly expressed
on endothelial cells and muscle cells. MAC (C5b-9) is formed as
a result of complement activation. It is not expressed in normal
muscles. MHC class I and class II are strongly expressed in
inflammatory myopathies, independently of inflammatory infiltrates [25–28]. MHC class I, class II and MAC are also expressed in
primary Sjögren’s syndrome with signs of subclinical myositis [29].
MHC class I and class II have also been found in muscle biopsies
from patients with RA [30]. MAC has been found in muscles in
juvenile dermatomyositis [31]. These markers are rarely expressed
in significant amounts in muscle biopsies from healthy persons [32].
Muscle weakness is also known to occur in juvenile idiopathic
arthritis (JIA) [33, 34]. This has been much less studied than
in adults, but the mechanisms are probably the same [35–37].
We are not aware of any study on muscle structure in children
with JIA. In the present study, muscle biopsies in children and
teenagers with JIA were examined and the findings correlated to
muscle strength. The results were compared with those for control
groups of healthy persons. The aim of the study was to analyse
if there are signs of muscle inflammation, vasculitis, type II muscle
fibre hypotrophy, or neuropathy in JIA, as have been found in
adult RA.
Material and methods
Patients
Patients were selected from a county in Sweden with 400 000
inhabitants. All children and teenagers with diagnosed active JIA
between 7 and 18 yr of age (n ¼ 26) were asked to participate in the
study, and 15 of them gave informed consent. Eight were girls and
seven were boys. Their ages ranged between 9.5 and 19 yr (mean
age 16.1 yr). Eight had oligoarthritis, six polyarthritis and one
monoarthritis. Individual data are given in Table 1.
Control groups
As a reference for muscle biopsies, samples taken from the
gastrocnemius muscle in 33 healthy young volunteers (30 women
1547
and three men) aged 18–23 yr (mean age 21.8 yr) were used. This
group was first examined to serve as controls in a different, hitherto
unpublished study. All were physiotherapy students. For ethical
reasons it was not considered appropriate to take biopsies from
age-matched healthy children.
For the strength measurements, we used age-related reference
values from healthy children and young adults aged 7–30 yr for
isometric strength (n ¼ 196) [38, 39] and aged 9–34 yr for isokinetic
strength (n ¼ 120) [40, 41].
Muscle biopsy
Biopsies were obtained from the anterior tibial muscle using local
anaesthesia and the semi-open conchotome biopsy technique
[42]. A standard histopathological examination was carried out
for all biopsies. Serial sections (more than 100 sections) were
analysed by light microscopy. In the control group, biopsies from
the gastrocnemius muscle were examined in a similar way.
Routine staining was performed after formalin fixation and
paraffin embedding. Stainings were carried out with Mayer’s
haematoxylin–eosin, Weigert’s haematoxylin–van Gieson and
Weigert’s elastin–van Gieson. Frozen specimens were stained
for myofibrillar adenosine triphosphatase (after preincubation
at pH 9.4 and 4.6), NADH tetrazolium reductase, phosphorylase
and acid phosphatase. A modified Gomori trichrome, Ehrlich’s
haematoxylin–eosin and Weigert’s haematoxylin–van Gieson were
also used on the frozen material. Periodic acid–Schiff (PAS) was
used for staining glycogen and oil red O for lipids.
Immunohistochemical stainings were made on 6 mm thick frozen
sections for analysis of cell surface markers with monoclonal
antibodies. Mouse monoclonal antibodies from Dako (Glostrup,
Denmark) were used: MHC class I (HLA-ABC M736, IgG2a,
1:100), MHC class II (HLA-DR M704, IgG2a, 1:50) and MAC
(anti-human C5b-9 M777, aE11, 1:25).
The following criteria were used for evaluation of abnormal
expression of inflammatory markers. MHC class I (on muscle
fibres): expression involving the total circumference of the muscle
fibre membrane in parts of the biopsy. MHC class II (on
capillaries): dense accumulations of capillary expression in isolated
parts of the biopsy. MAC: expression in capillaries. Grading
of expression was made according to scales earlier described
[29, 43]. The scales were validated in muscle biopsies from normal
controls [32].
The fibre types and fibre areas were measured with the TemaÕ
system (CheckVision ApS, Hadsund, Denmark). ATPase staining
at pH 4.3, 4.6 and 9.4 was used to differentiate between fibre types,
and an antibody against the sarcolemmal protein merosin was used
TABLE 1. Basic data of the patients with JIA
Patient
Sex
Age (yr)
Disease
duration (yr)
Height (cm)
Weight (kg)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
F
F
F
F
F
F
F
F
M
M
M
M
M
M
M
9.5
11.3
15.1
15.5
16.4
17.2
18.2
19.2
14.2
16.7
16.8
16.8
17.2
17.3
19.2
4
4
8
1
2
4
6
5
10
7
11
3
3
8
9
132
160
143
162
166
174
166
166
167
163
166
176
173
185
170
29
41
36
46
66
60
69
49
48
65
52
66
74
69
52
Disease subgroup
Oligoarticular
Oligoarticular
Polyarticular
Polyarticular
Oligoarticular
Polyarticular
Polyarticular
Oligoarticular
Monoarticular
Oligoarticular
Oligoarticular
Oligoarticular
Oligoarticular
Polyarticular
Polyarticular
Arthritis in
examined leg
Treatment
No
No
Yes
Yes
No
No
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
NSAID
NSAID
CS, NSAID, SSZ, D-Pen
NSAID
NSAID
NSAID
NSAID, AU
NSAID
ASA
ASA
NSAID, AU
NSAID, AU
NSAID, SSZ
NSAID, MTX
CS, NSAID, SSZ, D-Pen
F, female; M, male; CS, corticosteroid; D-Pen, D-penicillamine; ASA, acetylsalicylic acid; AU, auranofin; SSZ, sulphasalazine; MTX, methotrexate.
1548
H. Lindehammar and B. Lindvall
to delineate fibre areas. The numbers, percentages and mean areas
of fibre types I, IIA, IIB and IIC were measured. In each biopsy
between 90 and 265 muscle fibres were analysed. Because of the
small amount of muscle tissue in the biopsy, the muscle fibre
analysis could not be reliably performed for two patients.
All biopsies were prepared at the same laboratory, using the
same methods for patients and controls. All evaluations of the
muscle biopsies were made by an experienced muscle pathologist
(BL) with the same criteria for patients and controls. The following
findings were classified as minimal changes: the presence of some
centrally positioned nuclei in muscle cells; the presence of some
atrophic muscle fibres; and abnormal variation in fibre size (based
on experience).
for the appropriate age and sex, and in standard deviations from
the mean.
Muscle biopsy
Structure. Out of the 15 biopsies, four were considered normal
with no pathological changes on visual examination. Two biopsies
showed signs of mild inflammation, with small perivascular
infiltrates of inflammatory cells (Fig. 1). Eleven biopsies, including
those with cell infiltrates, showed increased variability of the
muscle fibre diameter or presence of some atrophic fibres or
centrally placed nuclei. These findings were classified as nonspecific minimal changes. In the healthy control group, none had
perivascular infiltrates and 7/33 showed minimal changes.
Muscle strength
The test procedures and positions were chosen to match reference
values [38–41]. Maximal isometric muscle strength in ankle
dorsiflexion was measured using a hand-held electronic dynamometer (Myometer; Penny and Giles, Christchurch, UK). The
maximal voluntary strength was measured by the breaking force
technique. The child sat with the knee in 90 flexion and the foot in
neutral position. The transducer head was applied on the dorsal
aspect of the foot proximal to the metatarsophalangeal joints.
Force was applied until the resistance was lost. Three measurements were made and the peak value was used for presentation.
The isokinetic muscle strength of ankle dorsiflexion was measured
using a CybexÕ II dynamometer. The position was the same as for
isometric strength measurement. Maximal developed torque was
measured at a constant angular velocity of 30 /s. Two measurements were made and the peak value was used. The strength
measurements were made on the same leg as the biopsy and in all
cases before the biopsy procedure.
Nerve conduction study
A nerve conduction study was carried out on the non-dominant
leg. The peroneal nerve was tested for motor nerve conduction
velocity, motor response amplitude and distal latency. The sural
nerve was tested for sensory nerve conduction velocity and sensory
nerve action potential.
Study design
Fibre type composition. The mean frequency of type I
fibres in the patient group was 75%. The subgroup of patients
with polyarthritis had a significantly lower percentage of type I
fibres than the subgroup with mono/oligoarthritis (66 vs 80%,
P ¼ 0.0017).
Fibre type area. The mean area of type I fibres in the patient
group was slightly but not significantly lower than that in the
control group. The mean area of type IIA fibres in the patients
was slightly but not significantly higher than in the control group
(Figs 2 and 3). For 14 of 15 patients the mean area of type I fibres
were lower than the mean area of type IIA fibres. The quotient
of the mean areas of type I and type IIA fibres was significantly
lower in the patient group compared with the control group
(77 vs 99%, P ¼ 0.0014). This difference was most pronounced for
the older patients and especially in males. Only one patient had
smaller type IIA fibres than type I fibres (case 2). Apart from this,
there were no signs of type II fibre hypotrophy. The quotient of
the mean areas of type IIA and IIB fibres was close to 100% in
both patients and controls. Type IIC fibres were not found in
any patient but were found in two of the healthy controls.
Immunohistochemistry. Four of the 15 patients showed
significant expression of MHC class II. This was significantly
(P ¼ 0.0143) more than in the control group (0/33). Two patients
with cellular infiltrates did not have increased expression of MHC
class II. For MHC class I and MAC the differences between
patients and controls were not significant.
This was a cross-sectional observational study.
Muscle strength
Statistical methods
To compare the patient group with the control group, a nonpaired, two-tailed t test was performed. To evaluate the relationship between muscle fibre variables and strength, a linear
regression model was used. Qualitative data were analysed in
2 2 contingency tables using Fisher’s exact test. A P value of
less than 0.05 was considered significant.
The study was approved by the ethics committee of the
University Hospital, Linköping (registration numbers 87110 and
97140).
Results
Individual values for the patients and corresponding results for
the control group are presented in Tables 2 and 3. Muscle strength
in children is dependent on age and gender. Strength values
were compared with the reference group and expressed as a percentage of the expected value (the mean of the reference group),
For the patient group, both isometric (P ¼ 0.018) and isokinetic
(P ¼ 0.008) strength were significantly reduced compared with the
reference group. For three of the 15 patients, isometric strength
was outside the normal range (2 S.D.). For isokinetic strength,
this was found in 1/15 patients.
Relationship between muscle strength and
muscle structure
There was a significant positive correlation between mean areas
of type I muscle fibres and isometric strength (P ¼ 0.0315) and
between the mean area of type IIA fibres and isometric
(P ¼ 0.0147) strength. There was no significant correlation between
muscle strength and the proportion of type I fibres or strength
and the quotient between areas of type I and type IIA fibres.
Statistically, we found no significant correlation between strength
and abnormal findings in the muscle biopsy, but 2/3 patients with
muscle strength below normal limits (below 2 S.D.) had cellular
infiltrates in the muscle biopsy. The disease subgroup or the
167
215
148
256
257
368
327
246
330
363
355
371
407
421
294
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
Patient mean (S.D.)
Control mean (S.D.)
P
95
107
51 (<2 S.D.)
80
69
94
83
62 (<2 S.D.)
132
93
85
98
90
92
63 (<2 S.D.)
86
100
0.018
%
8.5
11.4
5.9
20.5
25.1
17.4
13.0
13.6
22.5
23.7
21.7
26.2
25.4
25.9
16.5
Nm
77
88
30 (<2 S.D.)
95
114
79
57
59
112
89
80
99
94
96
59
82
100
0.008
%
Isokinetic strength
18
18
27
25
19
23
21
8
16
9
19
32
25
20 6.7
33 12.2
73
81
81
91
81
57
75
75 9.0
53 15.3
Type IIA (%)
82
80
63
69
75
68
Type I (%)
0
11
0
5 4.3
14 11.8
6
11
3
0
0
2
10
6
6
9
Type IIB (%)
Fibre type composition
Table shows muscle fibre areas and percentages of the different fibre types. Values outside 2 S.D. are in bold type.
N, newton; Nm, newton metre; n.s., not significant.
N
Patient
Isometric strength
TABLE 2. Strength in absolute values and as a percentage of the mean of the reference group
4495
2563
4203
3158 1076
3620 855
n.s.
2469
2508
3801
5610 (>þ2 S.D.)
2343
2464
1917
2511
2746
3420
Type I (mm )
2
7376 (>þ2 S.D.)
4612
8329 (>þ2 S.D.)
4520 2091
3758 1150
n.s.
4431
4525
5950
6989 (>þ2 S.D.)
2404
1726
2402
2717
3394
3904
Type IIA (mm2)
Fibre type area
3483 1180
3681 1024
n.s.
3346
3965
4375
5683
1703
2418
2818
3022
4019
Type IIB (mm2)
61 (<2 S.D.)
56 (<2 S.D.)
50 (<2 S.D.)
77 25
99 17.1
0.0014
56 (<2 S.D.)
55 (<2 S.D.)
64 (<2 S.D.)
80
97
143 (>þ2 S.D.)
80
92
81
88
Fibre area ratio:
type I/type IIA (%)
Muscle involvement in JIA
1549
H. Lindehammar and B. Lindvall
1550
TABLE 3. Morphology and immunohistochemistry of muscle biopsies
Morphology
Patient
Minimal changes
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
Patient group
Control group
P
Yes
No
No
No
Yes
Yes
Yes
Yes
Yes
No
Yes
Yes
Yes
Yes
Yes
11/15
7/33
0.0462
Other
Small perivascular infiltrates
Small perivascular infiltrates
2/15
0/33
MHC class I
MHC class II
Negative
Negative
Negative
Positive
Negative
Negative
Negative
Negative
Negative
Negative
Negative
Negative
Negative
Negative
Negative
1/15
2/33
n.s.
Positive
Positive
Negative
Negative
Negative
Negative
Negative
Negative
Positive
Positive
Negative
Negative
Negative
Negative
Negative
4/15
0/33
0.0143
MAC
Negative
Negative
Positive
Negative
Negative
Negative
Negative
Negative
Negative
Negative
Negative
Positive
Negative
Negative
Negative
2/15
1/33
n.s.
n.s., not significant.
FIG. 1. Muscle biopsy from one of the patients showing perivascular inflammation. Haematoxylin–eosin staining.
presence of local arthritis did not have a significant effect on the
muscle biopsy findings.
Nerve conduction study
One of the patients had a sural nerve conduction velocity just
below the lower limit. This was not regarded as significant. The
remaining results were normal.
Discussion
In this study we found changes in the muscles of patients with JIA.
The majority of the muscle biopsies showed minor changes, most
commonly increased variation in muscle fibre diameter and the
presence of some atrophic fibres. These are unspecific changes of
unknown significance. We found no correlation between these
small structural changes and muscle function or disease subgroup.
Minimal biopsy changes are sometimes seen in healthy persons
[22]. This was the case in 21% of our control group.
Muscle involvement in JIA
1551
FIG. 2. Muscle biopsy showing smaller area of type I fibres (light) compared with type II fibres (dark) stained for ATPase after
preincubation at pH 9.4.
FIG. 3. The same muscle biopsy as in Fig. 2 stained for ATPase at pH 4.6, showing type I fibres darkly stained and type II fibres
lightly stained. Type I fibres are smaller than type II fibres.
H. Lindehammar and B. Lindvall
Perivascular cellular infiltrates are a sign of inflammation and
are not a normal finding in muscle biopsies. This pathological
result was found in biopsies from two patients. Both had reduced
muscle strength. One of these patients had severe chronic polyarthritis with muscle weakness and hypotrophy. The other patient
had moderately active oligoarthritis with reduced muscle strength.
None of them showed other signs of vasculitis or myositis.
In adult RA, both myositis and vasculitis are known to occur.
Miro et al. [9] found myositis in 8/21 and vasculitis in muscle
biopsies in 1/21 RA patients with muscle weakness. Halla et al. [10]
found myositis in 13/31 RA patients, most frequently in systemic
disease, and vasculitis in 2/31 patients. The expression of MHC
class II in four of the patients in the JIA group in the present
study may be a sign of inflammatory myopathy. This is further
supported by the finding of perivascular cellular infiltration in
two patients. The patients with cellular infiltrates were not the
same as those who had positive MHC class II expression. This is
in agreement with results from previous studies of inflammatory
myopathies [25, 26, 29], in which muscle fibres express MHC class I
and class II antigens independently of inflammatory infiltrates.
The small cellular infiltrates were not examined for expression
of inflammatory markers. Expression of MHC class I and class II
is common near inflammatory infiltrates. The sections of the
muscle biopsy specimen were not the same in the analysis of
morphological changes and MHC expression. The four patients
with positive expression of MHC class II antigens were young but
no correlation with disease subgroup or muscle strength was found.
In the present study of children and teenagers with JIA we did
not find signs of type II muscle fibre hypotrophy, as might have
been assumed from studies on adults with RA, which have revealed
such hypotrophy. Halla et al. [10] found type II fibre hypotrophy
in 12/16 RA patients without symptoms of myopathy. Miro et al.
[9] found the same in 11/21 RA patients with symptoms of
myopathy. The reduced quotient between the mean area of type I
and type IIA in the patients compared with the control group may
be a sign of relative type I fibre hypotrophy. The reason for this
difference is not obvious. Selective type I fibre hypotrophy has
previously been described in the quadriceps muscle after anterior
cruciate ligament injuries [44], but is otherwise not a common
finding. The selective fibre hypotrophy could not be solely due to
immobilization, since other lesions to the knee do not cause this
type of hypotrophy. The reason for this may be reflex inhibition.
In the literature we have not found evidence for any difference in
the relative areas of type I and type IIA fibres due to the age of
children and adolescents [45, 46]. It is, however, possible that the
difference in fibre area ratio between patients and controls is
an effect of the relatively large type II fibres in the male patients.
It is known that type II fibres are larger than type I fibres in
adult healthy males, particularly in the anterior tibial muscle.
Other studies in adults in which muscle fibre areas in the anterior
tibial muscle have been measured reported a quotient between
mean area of type I and type II fibres ranging from 49 to 67%
[19, 22, 47]. Most of the persons in the control group in the current
study were women and the biopsies were taken from another
muscle. There were, however, no signs of selective hypotrophy
of type II fibres in the JIA group.
In the present study, the patients with JIA had more type I fibres
than the controls, probably because the biopsies were obtained
from different muscles. The difference in fibre type composition
could also be explained by the difference in age between the groups.
Previous studies have indicated that in the anterior tibial muscle
about 75% of the muscle fibres are of type I [22, 48]. The children
with polyarthritis had a lower percentage of type I fibres than the
other JIA patients. This could be an effect of less activity in
children with polyarthritis. It is known that the distribution of fibre
types and fibre area varies in different parts of the muscle [49, 50].
This may also explain the difference between patients and controls.
The patients’ muscle strength correlated to mean muscle fibre
area. This is expected since muscle force is partly the effect of the
amount of contractile myofilaments. In this study strength was
reduced in proportion to mean muscle fibre area. This implies that
part of the weakness is caused by a reduction in muscle fibre area.
This is further supported by the fact that children with JIA also
have reduced muscle thickness, related to muscle weakness in the
knee extensor muscle [34].
The fibre area was not significantly affected by the presence of
active local arthritis in the same leg, as could have been expected
from reflex inhibition. The results could, however, have been
confounded by the fact that all boys had arthritis in the examined
leg, and older boys usually have larger muscle fibre areas than
girls. Nor did we find any correlation between immunohistochemical changes in muscle biopsies and local arthritis. Of the two
patients with cellular infiltrates, both had local arthritis. The
material is too small to draw certain conclusions from.
The nerve conduction study did not show any obvious signs
of sensory neuropathy or mononeuropathy in the leg, as have
been found in adults with RA. One previous study also failed to
reveal peripheral nerve involvement in JIA [51]. Consequently,
nerve dysfunction is probably not responsible for the muscle
dysfunction in JIA.
The main limitations of the present study are the small number
of patients, the lack of a strictly age-matched control group for
muscle biopsies, and the fact that the biopsies were not obtained
from the same muscle in patients and controls. Muscle biopsies
were not obtained from age-matched normal children and teenagers as this was considered unethical. The biopsy procedure is
somewhat painful and not appreciated by younger children. The
patients in the present study all volunteered; it was not possible
to persuade all to participate. The 15 participants in the study
are, however, a representative sample of children and teenagers
with JIA. The biopsies from the control group were taken from
a different muscle and were originally obtained for other studies
(unpublished). This could explain the difference in fibre type
composition and the difference in relative fibre type area between
the groups. The presence of inflammatory cell infiltrates is not
a normal finding. The occurrence of minimal changes and the
expression of inflammatory markers are not supposed to be
different in various muscles.
In conclusion, this study has shown that children and teenagers
with JIA have reduced muscle strength and changes in muscle
structure and muscle immunology, as in adult RA, with the
difference that patients with JIA show no signs of neuropathy or
selective type II muscle fibre hypotrophy.
Key messages
Rheumatology
1552
Many children with JIA have reduced
muscle strength and structural and
immunological changes in muscles.
Selective type II muscle fibre hypotrophy
or neuropathy is not as common as in
adult RA.
Acknowledgements
Special thanks to Professor Björn Gerdle for letting us use his
muscle biopsies from healthy physiotherapy students, and to
laboratory technicians Lisbeth Lindvall and Gunnvor Sjöö for
their skilful work with the muscle biopsies. The study was
supported by grants from The County Council of Östergötland,
The Foundation Samariten, The Foundation Karlfeldts minne
and The King Gustaf V Foundation.
The authors have declared no conflicts of interest.
Muscle involvement in JIA
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