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The effectiveness of treating juvenile dermatomyositis with methotrexate and aggressively tapered corticosteroids.

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Vol. 52, No. 11, November 2005, pp 3570–3578
DOI 10.1002/art.21378
© 2005, American College of Rheumatology
The Effectiveness of Treating Juvenile Dermatomyositis With
Methotrexate and Aggressively Tapered Corticosteroids
A. V. Ramanan, N. Campbell-Webster, S. Ota, S. Parker, D. Tran, P. N. Tyrrell, B. Cameron,
L. Spiegel, R. Schneider, R. M. Laxer, E. D. Silverman, and B. M. Feldman
Objective. Childhood dermatomyositis (DM) is
often a chronic disease, lasting many years. It has
traditionally been treated with long-term corticosteroid
therapy; side effects are often seen. For more than a
decade, methotrexate (MTX) has been safely used for
the treatment of juvenile arthritis. Here, we report use
of MTX as first-line therapy for DM, along with aggressively tapered corticosteroids, in an attempt to reduce
treatment-related side effects.
Methods. We studied an inception cohort of 31
children with DM who were rigorously followed up in
our myositis clinic, and compared them with a control
group of 22 patients with incident cases of juvenile DM
who received treatment just before we instituted a policy
of first-line therapy with MTX. The mean starting
dosage of MTX in the study group was 15 mg/m2/week.
Results. Both groups had similar improvement in
strength and physical function; however, the median
time during which patients in the study group received
corticosteroids was 10 months, compared with 27
months for controls (P < 0.0001). As a result, the
cumulative prednisone dose in the study group was
approximately half that in the control group (7,574 mg
versus 15,152 mg; P ⴝ 0.0006). The study group had
greater height velocity during the first year of treatment
and a smaller increase in the body mass index over the
first 2 years. In the control group, the relative risk of
cataracts developing was 1.95 (95% confidence interval
1.05–4.17). Side effects of MTX were rarely observed.
Conclusion. Use of MTX in conjunction with an
aggressively tapered course of prednisone may be as
effective as traditional long-term corticosteroid therapy
for children with DM, while decreasing the cumulative
dose of corticosteroids.
Juvenile dermatomyositis (DM) is a chronic multisystem disease of presumed autoimmune origin that
primarily affects skin and muscle. In western populations, the incidence of juvenile DM is ⬃2–3 per 1 million
children per year (1–3). Although the outcomes of
juvenile DM have improved over the last few decades,
the disease is still associated with significant morbidity in
a proportion of patients (4,5). For many patients, juvenile DM follows a chronic course. According to a recent
retrospective multicenter Canadian study of children
with juvenile DM, 35% of the children (23 of 65) were
still receiving medication for persistent disease activity
after a median followup of 7 years (5).
No prospective randomized study has shown the
efficacy of any immunosuppressive agent for the treatment of juvenile DM. The mainstay of therapy for
juvenile DM has been long-term corticosteroid treatment, which, although efficacious, is associated with
significant side effects. The standard approach to treatment of juvenile DM has been use of high doses of oral
corticosteroids, with slow tapering over at least 2 years
(6). The major limitations of this treatment are side
effects and, in some patients, incomplete response.
The major side effects of corticosteroids include
growth delay, osteoporosis, avascular necrosis, cataracts,
and hypertension. In 2 studies (7,8), side effects of
corticosteroids were observed in 32–41% of adult patients with DM or polymyositis. Although the relationship between cumulative doses of corticosteroids and
these side effects remains unclear, in general the side
A. V. Ramanan, MD, N. Campbell-Webster, MD, S. Ota,
BSc, S. Parker, BScN, D. Tran, P. N. Tyrrell, BSc, MSc, B. Cameron,
MD, FRCPC, L. Spiegel, MD, FRCPC, R. Schneider, MD, FRCPC,
R. M. Laxer, MD, FRCPC, E. D. Silverman, MD, FRCPC, B. M.
Feldman, MD, MSc, FRCPC: Hospital for Sick Children, University of
Toronto, Toronto, Ontario, Canada.
Address correspondence and reprint requests to B. M. Feldman, MD, MSc, FRCPC, The Hospital for Sick Children, University of
Toronto, 555 University Avenue, Toronto, Ontario M5G 1X8, Canada. E-mail:
Submitted for publication June 4, 2004; accepted in revised
form July 21, 2005.
effects of corticosteroids are thought to be related to the
dose and duration of therapy. It is increasingly recognized that even prolonged low-dose therapy may cause
some of these side effects (9).
Methotrexate (MTX) is an immunosuppressive
agent that has been used successfully in a wide variety of
pediatric rheumatic diseases (10,11). Experience gained
from the use of MTX in childhood arthritis has shown
that low-dose therapy is safe, with little reported longterm toxicity. In small, uncontrolled, retrospective studies (12–16), MTX was suggested to be beneficial as
adjunctive therapy in patients with juvenile DM refractory to corticosteroids or in patients dependent on
corticosteroids (12–16). Recently, Fisler et al conducted
a review of the medical records of 35 children with
juvenile DM, 23 of whom were started on a regimen of
MTX after failing to respond within 6 weeks to corticosteroids. This cohort was considered to have had a good
response to treatment and a decreased incidence of
calcinosis (17). At followup, 5 patients (14%) had mild
calcinosis; this rate is lower than the rate of ⬃33%
observed in other studies (18).
As a result of these studies, there has been
interest in starting MTX earlier in patients with disease
refractory to corticosteroid treatment, similar to the
early use of MTX or azathioprine in adult DM. However, corticosteroids remain the initial treatment for the
majority of patients with juvenile DM. For example,
Wulffraat et al surveyed 50 pediatric rheumatology
centers in 30 countries representing the Paediatric
Rheumatology International Trials Organization. They
found that in all centers corticosteroids were used
initially, and that only 17 centers considered using MTX
adjunctively as a first-line agent (19). There are no
controlled studies of MTX as a first-line agent, with or
without concomitant steroid therapy, in the treatment of
patients with juvenile DM.
Our research question was as follows: does treatment of juvenile DM with MTX and an aggressively
tapered course of corticosteroids result in a decreased
cumulative dose of corticosteroids, while not compromising treatment efficacy, when compared with the
standard regimen in which corticosteroids are tapered
more slowly? We hypothesized that our approach of
using MTX along with an aggressively tapered course of
corticosteroids is as effective as the traditional regimen,
results in a lower cumulative dose of corticosteroids and
fewer corticosteroid-related adverse effects, and is safe
in terms of MTX side effects.
We present the results of our cohort study, in
which patients treated with MTX in combination with a
course of aggressively tapered corticosteroids were compared with historical controls from our institution who
were treated according to the traditional approach of a
lengthy course of corticosteroids.
Patient population and study design. We performed a
retrospective cohort study of 31 consecutive patients with
incident cases of juvenile DM who were seen in our clinic since
June 1997. We compared these patients with 22 consecutive
control patients with incident cases of juvenile DM who were
seen in our clinic during the preceding period, January 1993 to
May 1997. The start date of January 1993 was chosen because
at that time we began using a more comprehensive followup
form at the clinic. All 53 patients underwent the same
protocol-based followup in the myositis clinic at the Hospital
for Sick Children (Sick Kids). The study was approved by the
Research Ethics Board at Sick Kids.
Inclusion and exclusion criteria. All children in whom
probable or definite juvenile DM was diagnosed at Sick Kids
were included (20,21). Patients in whom a diagnosis was made
and for whom therapy began before referral to Sick Kids and
those children who had myositis as part of an overlap syndrome were excluded (Figure 1).
Sick Kids myositis clinic. Since 1991, all patients with
juvenile DM or other idiopathic inflammatory myopathies who
were seen at Sick Kids have been followed up in a separate
subspecialty clinic. Staff members attending the juvenile DM
clinic include a rheumatologist, a nurse specialist, a dedicated
physiotherapist (and more recently a physiotherapy practitioner), a dedicated nutritionist, and, most recently, a neurologist specializing in neuromuscular disorders. Patients are
attended to by the house staff rotating through the clinic, who
are supervised by the faculty. All patients are assessed and
treated according to a defined protocol that has been in place
since the inception of the clinic. Collaborating members of the
divisions of dermatology, neurology, and ophthalmology see all
of the patients early in the course of their disease. All clinic
and laboratory data are prospectively collected and stored in a
dedicated database.
Treatment. The study group received MTX (10–20
mg/m2/week [maximum dosage 25 mg/week]) and prednisone
(2 mg/kg/day [maximum dosage 75 mg/day]). Prednisone initially was administered in 3 divided doses and then was
consolidated, over the first 6 weeks, into a single daily dose. At
6 weeks, if the level of muscle enzymes in serum was reduced
compared with that at the time of diagnosis and the patient had
improved clinically, the prednisone dose was tapered by ⬃10%
every 2 weeks. Weaning patients off prednisone was done
according to protocol; however, patients were not weaned if
disease was not well controlled. If there was a flare of
symptoms, the dose of prednisone was increased until control
was achieved. Subjects were evaluated every 2 weeks initially;
the frequency of visits then decreased to every 4 weeks, then
every 6–12 weeks over the first year. Initially, MTX was
administered orally; if required, the route of administration
was changed to subcutaneous. Children were given MTX
Figure 1. Disposition of children with juvenile dermatomyositis
(JDM) seen at The Hospital for Sick Children (HSC) during the study
period. JPM ⫽ juvenile polymyositis.
subcutaneously if nausea and/or vomiting occurred as a side
effect or if a dosage in excess of 15 mg/week was required.
The control group received prednisone at a dosage of
2 mg/kg/day. Prednisone initially was administered in divided
doses and then was consolidated, over the first 6 weeks, into a
single daily dose. The patients were then weaned off prednisone, with tapering at a rate of ⬃10% every month, taking
into account the clinical response.
In children presenting with severe weakness, dysphagia, dysphonia, or vasculitic skin ulcers (ulcerative juvenile
DM), additional medications including cyclophosphamide,
cyclosporine, pulse intravenous methylprednisolone (30 mg/kg,
to a maximum dosage of 1,000 mg/day for 3 days), and/or intravenous immunoglobulin (IVIG) were added at the onset of
treatment, at the discretion of the attending rheumatologist.
Hydroxychloroquine and IVIG were also used in children in
whom skin rash persisted despite other therapy.
Followup. All control patients were followed up for 4
years (1,056 patient-months). The study patients were followed
up for an average of 34.6 months. Of the 31 study patients, 12
were followed up for 4 years, 2 were followed up for 3–4 years,
12 were followed up for 2–3 years, 2 were followed up for 1–2
years, and 3 were followed up for ⬍1 year (1,073 patientmonths).
Assessment and outcome measures. The primary outcome measure was the time to discontinuation of prednisone,
as well as the cumulative corticosteroid dose (including prednisone and intravenous methylprednisolone) and the presence
of corticosteroid side effects (see below) at 3, 6, 12, 18, 24, 36,
and 48 months of followup.
Efficacy, as assessed by muscle power, the Childhood
Health Assessment Questionnaire (C-HAQ; a validated measure of physical disability in juvenile DM) (22,23), the revised
American College of Rheumatology (ACR) functional class
(24), presence of skin rash, time to development of calcinosis,
and time to flare, was also examined. At each followup visit,
the presence of calcinosis was determined clinically, and
nailfold capillary microscopy was performed. Because muscle
enzyme levels normalize rapidly at the onset of therapy (as
indeed they did in both of our groups) and are not well
correlated with other measures of disease activity, we did not
use muscle enzyme levels for the purposes of this study.
We examined corticosteroid side effects by calculating
the change in body mass index (BMI) as a proxy for cushingoid
obesity, height velocity, time to development of cataracts, and
time to development of spinal fractures. Bone mineral density
studies were not routinely performed in our control patients
and therefore could not be used to compare the 2 treatment
strategies. Significant gastrointestinal (GI) toxicity (defined as
toxicity leading to cessation of therapy) was used as a measure
of MTX toxicity.
The muscle power of all patients was scored by the
physician at each clinic visit, using the Oxford Medical Research Council grading system (25). Additionally, the clinic
physiotherapist scored each of the major muscle groups using
dynamometry (using a modified sphygmomanometer) (26,27).
Disease flares were defined as active disease of skin or
muscle requiring increased therapy with corticosteroids and/or
additional medications. Liver-related enzyme levels (alanine
aminotransferase, aspartate aminotransferase) were considered to be abnormal if they were twice the upper limit of
Statistical analysis. Because both groups were not
followed up for the same length of time, we used survival
analysis to answer our primary question. The time to event end
points (e.g., discontinuation of corticosteroids, time to flare,
time to development of cataract) were plotted using the
Kaplan-Meier technique, and the 2 treatment groups were
compared using the log rank test; relative risks (RRs; relative
hazards) were calculated using proportional hazards regression
models. Other comparisons between the groups used repeatedmeasures analysis of variance and the 2-sample t-test. When
the assumptions for parametric testing were not met, nonparametric testing was substituted. Because there are no normal
standards for children for the muscle dynamometry testing that
we used, we calculated the change from baseline for each
subject as an absolute percent change (compared with the
maximum score of 300). The analyses were carried out using
Data Desk statistical software version 6.2 (Data Description,
Ithaca, NY) and the JMP statistical package version 5.0.1a
(SAS Institute, Cary, NC).
Table 1.
Baseline characteristics of patients in the 2 groups*
Mean age at diagnosis, years
No. boys/no. girls
East Indian
Native Canadian
Definite dermatomyositis
Probable dermatomyositis
Mean body mass index, kg/m2
Mean weight, kg
Mean muscle power in weakest muscle group, kg
Mean C-HAQ score
Presence of nailfold abnormalities
Mean ACR functional class
Median prednisone starting dosage, mg/kg/day
Study patients
(n ⫽ 31)
Control patients
(n ⫽ 22)
* Except where indicated otherwise, values are the number of patients. The determination of definite and
probable dermatomyositis was based on the criteria described by Bohan and Peter (20,21). C-HAQ ⫽
Childhood Health Assessment Questionnaire; ACR ⫽ American College of Rheumatology.
Demographics. The 2 groups comprised 31 study
patients and 22 control patients, respectively. The baseline characteristics of the 2 groups, including age at
diagnosis, sex, and ethnicity, were similar (Table 1).
Baseline function and strength, as measured by the
C-HAQ, median muscle strength in the weakest muscle
group, and revised ACR functional class, were also
similar in the 2 groups. All patients in both groups had
evidence of skin disease at the time of diagnosis of DM.
Cumulative dose of corticosteroid, time to discontinuation of corticosteroids, and corticosteroid side
effects. The median starting dose of corticosteroid was
different in the 2 groups (1.81 mg/kg in the study group
versus 2.00 mg/kg in controls; P ⫽ 0.01). These differences may reflect the fact that the study group was
somewhat older and heavier at baseline and therefore
more likely to reach the maximum dosage of 75 mg of
prednisone per day.
Use of the described protocol resulted in significantly less exposure to prednisone in the study patients
than in the control patients. In most study patients it was
possible to closely follow the tapering protocol, but there
was some variability in the time to full discontinuation of
prednisone (Figure 2). The median time to discontinuation of prednisone was 10 months in the study group,
compared with 27 months in the control group (P ⬍
0.0001, RR 0.41, 95% confidence interval [95% CI]
0.29–0.57). The average cumulative dose of cortico-
steroids (expressed as milligrams of prednisone) in the 2
groups, including only those patients in the study group
who were followed up for the full 4 years, was 15,152 mg
in the control group and 7,574 mg in the study group (P
⫽ 0.0006).
The average BMI at the time of diagnosis was
similar in the 2 groups (16.98 kg/m2 in the study group
Figure 2. Survival plot showing time to discontinuation of prednisone.
The y axis shows the proportion of subjects who were still receiving
prednisone at any point in time. The x axis shows the number of
months since starting therapy.
Table 2.
Change in muscle strength as measured by the physiotherapist, using muscle dynamometry*
Measure of muscle strength
Left hip abduction
Study group
Right hip abduction
Study group
Left hip extension
Study group
Right hip extension
Study group
Left hip flexion
Study group
Right hip flexion
Study group
Left shoulder abduction
Study group
Right shoulder abduction
Study group
Left shoulder flexion
Study group
Right shoulder flexion
Study group
Neck flexion
Study group
Left grip
Study group
Right grip
Study group
P for
6 months
12 months
24 months
* Values are the mean per group. The change from baseline for each subject was calculated as an absolute
percent change (compared with the maximum score of 300).
† From a repeated-measures analysis of variance model. In control patients, recordings of hip flexion and
neck flexion were not routinely obtained during the earlier (6 months) period.
versus 16.39 kg/m2 in the control group). At 1 year of
followup, the BMI had increased by an average of 4.7
kg/m2 in the control group, compared with an average
increase of 2.2 kg/m2 in the study group (F ⫽ 14.5, 1 df,
P ⫽ 0.0004), and over the first 2 years the BMI had
increased by 2.8 kg/m2 in the control group and by 2.0
kg/m2 in the study group (F ⫽ 6.67, 2 df, P ⫽ 0.002).
There were too few data to permit a meaningful comparison of the BMI at 3 and 4 years.
The height velocity at 1 year was significantly
different in the 2 groups. The control patients had an
average height velocity of 2.8 cm/year compared with an
average of 4.1 cm/year in the study group (P ⫽ 0.048).
The difference in height velocity was no longer discernible at 2 years of followup (both groups grew at the same
rate from year 1 to year 2).
Cataracts developed in 8 patients in the control
group and in 3 patients in the study group. Fortunately,
none of these cases has been vision-limiting or has
required therapy. The time to development of cataracts
was significantly shorter in the control group (RR 1.95,
95% CI 1.05–4.17, P ⫽ 0.03). Spinal fractures developed
in 2 control patients (at 3 months and 11 months,
respectively) and in 1 study patient (at 6 months).
Disease activity. During followup, changes in
disease activity as measured by the C-HAQ, muscle
Figure 3. Survival plot showing time to development of disease flare.
The y axis shows the proportion of subjects who were free of disease
flare at any point in time. The x axis shows the number of months since
starting therapy.
power, rash, and the revised ACR functional class were
similar in the 2 groups. By 12 months, the median
C-HAQ was 0 (normal function) in both groups, and
over the first 2 years there was no difference between the
groups in repeated measures of improvement (F ⫽ 1.3,
5 df, P ⫽ 0.27). Likewise, the improvement in functional
class was similar between the 2 groups over the first 2
years of followup (F ⫽ 0.72, 5 df, P ⫽ 0.61). The rate of
change in muscle strength is presented in Table 2.
All patients in both groups had a rash at the time
of diagnosis of DM and initiation of therapy. All patients
experienced subjective improvement during the first few
months of treatment. At 1 year, however, at least some
rash was noted clinically in 14 (47%) of 30 patients in the
study group (for whom adequate information was available) and in 9 (43%) of 21 control patients (P ⫽ 0.79).
At 2 years, 10 (50%) of 20 study patients and 7 (35%) of
20 control patients had some persistent or recurrent
rash. Rash was present at 3 years in 3 (33%) of 9 study
patients and in 4 (22%) of 18 control patients; the
numbers at 4 years were 2 (40%) of 5 study patients and
4 (24%) of 17 controls. The presence of rash was not
statistically significantly different between the groups.
During the followup period, calcinosis developed
in 5 control patients and 2 study patients. In the 5
control patients, calcinosis was first noticed clinically at
2, 12, 27, 32, and 44 months after initiation of treatment,
respectively. In the 2 study patients, calcinosis was first
noticed at 5 and 16 months, respectively. The time to
development of calcinosis was similar in the 2 groups
(for controls versus patients, RR 1.7, 95% CI 0.8–4.4).
Over the course of the study, 7 study patients and 7
control patients had disease flares. The time to development of a flare was similar in the 2 groups (RR 1.04,
95% CI 0.61–1.80). The time to development of a flare
in both groups is shown as a Kaplan-Meier survival plot
in Figure 3. There was no apparent difference between
the groups in the response to re-treatment following a
Additional medications. As shown in Table 3, 15
(48%) of 31 study patients and 6 (27%) of 22 control
group patients were also treated with IVIG (P ⫽ 0.12).
The number of patients receiving any additional immunosuppressive agent was similar in the 2 groups (55% of
study patients and 46% of controls; P ⫽ 0.50).
Both of the patients who were treated with
cyclophosphamide had ulcerative juvenile DM, characterized by necrotic skin ulcers presumed to be attributable to vasculitis. After receiving 7 monthly infusions of
cyclophosphamide, both patients were treated with
MTX. Although these 2 patients were treated similarly,
they were assigned to study and control groups based on
the period during which they were followed up (using
the intent-to-treat principle); exclusion of these 2 patients did not change our results.
Eight patients in the control group were treated
with hydroxychloroquine, compared with 6 patients in
the study group. Six of the control patients were eventually treated with MTX after demonstrating steroid
dependence and persistent disease activity.
MTX dosing and side effects. In the study group,
the mean starting dose of MTX was 15 mg (15 mg/m2/
week [0.56 mg/kg/week]; minimum 0.19 mg/kg/week,
maximum 1.0 mg/kg/week). The maximum dosage during treatment was, on average, 0.64 mg/kg/week (minimum 0.19 mg/kg/week, maximum 1.25 mg/kg/week). The
average dosage of MTX at the time of discontinuation of
Table 3.
Additional medications required by study subjects*
Intravenous immunoglobulin
Cyclosporin A
Total no. of subjects receiving
any of the above
15 (48.4)
1 (3.2)
1 (3.2)
1 (3.2)
6 (19.4)
17 (54.8)
6 (27.3)
1 (4.6)
8 (36.4)
6 (27.2)
10 (45.5)
* Values are the number (%). Not all study subjects were followed up
for 4 years. NA ⫽ not applicable.
in 3 patients while they were receiving MTX; these
infections included 1 case each of shingles, fungal vaginitis, and cellulitis of the metacarpophalangeal joint.
Unfortunately, because infections were not as carefully
tracked during the time period before MTX was introduced into the clinic, comparisons could not be made.
Kawasaki disease was diagnosed in 1 patient during
MTX therapy, and the patient was treated accordingly.
Figure 4. Survival plot showing time to discontinuation of methotrexate (MTX) for the study group patients. The y axis shows the
proportion of subjects who were still receiving MTX at any point in
time. The x axis shows the number of months since starting therapy.
prednisone was 0.53 mg/kg/week. When disease activity
was controlled and prednisone could be tapered, MTX
was also tapered, with the goal of determining the lowest
effective dosage. During additional followup (past the
study period), 18 of the 31 patients were able to discontinue MTX while disease was in complete remission.
The median length of time receiving MTX was 45.5
months (Figure 4). Seventeen of the study patients
received MTX parenterally (subcutaneously) at some
point during the course of treatment.
Elevations in the levels of liver-related enzymes
were observed in 6 study patients and 3 control patients
during followup. In 5 of the 6 study patients and in all 3
control patients, these elevations coincided with a flare
of disease activity and therefore likely represented muscle inflammation rather than hepatocellular injury. In 1
study patient MTX was discontinued because of persistently elevated levels of transaminase. A liver biopsy was
performed in that patient, which revealed nonspecific
inflammation. Therapy with MTX was not recommended, however, because the patient’s disease was
under good control with only corticosteroids. None of
the other patients discontinued MTX because of elevations in the levels of liver-related enzymes, and none has
developed any clinical signs of liver toxicity.
There were no other significant GI side effects in
any of the patients receiving MTX. Infections developed
Low-dose MTX along with a course of rapidly
tapered prednisone, when used as initial therapy for
juvenile DM, resulted in good control of disease activity
as well as a reduction in the cumulative dose of corticosteroids. This therapeutic approach was associated with
fewer corticosteroid side effects, and significant side
effects of MTX were not observed.
MTX appears to be safe for use as first-line
therapy in juvenile DM. The major concerns regarding
MTX include hepatotoxicity, an increased risk of infection, and GI upset (28). In our study, there was no
apparent increase in hepatotoxicity or severe GI upset in
the group receiving MTX. Overall, the levels of transaminase elevation did not differ between the 2 groups. One
patient receiving MTX discontinued the medication
because of persistently elevated transaminase levels, but
a liver biopsy revealed no significant pathology. Liver
biopsies were not warranted in any of the other patients
in the study.
In our study, patients were followed up for a
relatively short period of time. In the study group, we
were able to successfully wean patients off prednisone at
a much quicker rate than had been attempted in the
control group, and therefore the cumulative prednisone
dose and the median time receiving prednisone were
significantly less in the study group. Correspondingly,
there was less of an increase in BMI, greater height
velocity during the early period, and a decreased rate of
cataract development in the study group patients over
the first 2 years. However, it is unclear whether the
benefits of this new approach will continue. Also, some
patients with juvenile DM have been reported to experience slowly progressive late morbidity and disability
(29). It is possible that our MTX-treated patients will
have a different long-term experience than the traditionally treated group. Longer followup is required to identify possible long-term benefits of reduced prednisone
exposure, such as changes in bone density and fracture
It is certainly possible that not all of our patients
need additional early treatment with MTX; there may be
subgroups of patients who would tolerate rapid withdrawal of corticosteroids without any additional treatment. Indeed, a subgroup of 3 of 7 patients from British
Columbia who had mild disease were treated with
intravenous methylprednisolone infusions on a regular
schedule and never needed daily corticosteroids (30). In
fact, it is possible that MTX did not add any additional
benefit; we may have been able to treat control patients
with more rapid corticosteroid tapering without compromising their care. However, it is traditionally believed
that shorter courses of corticosteroids result in inadequate disease control and the development of complications (6,29). Our rationale for using MTX to treat all
new patients with juvenile DM was 2-fold: we currently
do not have accurate methods for determining which
patients with juvenile DM will have a milder disease
course, and MTX appears to be very safe when used in
low doses to treat rheumatic diseases.
It must be noted that our study patients were
treated more often with IVIG than were control patients, although the difference was not statistically significant. At our center we often use IVIG to treat
steroid-resistant disease (31). The aforementioned discrepancy is most likely attributable to undertreatment in
the control group due to a worldwide shortage of IVIG
products during that time period. However, it is certainly
possible that IVIG was used more often in the study
patients in response to features of disease activity (e.g.,
continued rash) that resulted from a decrease in the
amount of corticosteroids used.
Our results must be considered in light of potential limitations due to our study design. Several of the
control patients were eventually treated with MTX. Such
treatment represents a form of contamination: by including these children we may have underestimated the
potential steroid-sparing effect of MTX. Moreover, we
used historical controls, and this method may have
introduced bias. There may have been temporal changes
in the types of patients presenting to our clinic or
changes in other aspects of treatment rather than the
MTX protocol. These factors cannot be accounted for
unless contemporaneous controls are used. However,
our treatments were based on standardized protocols,
and data were carefully collected onto standardized
forms at the time patients were seen. Also, the same staff
at a single center followed up the 2 groups of patients.
We believe that we have minimized the potential bias
associated with comparisons using historical controls.
Our study should be considered a preliminary
step in the assessment of the role of MTX in the initial
management of juvenile DM. The results of our study
suggest that patients treated with MTX and a course of
aggressively tapered prednisone have less exposure to
corticosteroids and therefore may experience less associated toxicity. In conclusion, MTX in conjunction with
an aggressively tapered course of prednisone may be as
effective as traditional long-term corticosteroid therapy
while decreasing the cumulative dose of corticosteroids
in these patients.
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