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CHRISTEN-ZAECH ET AL
Nailfold capillaroscopy and DAS assessments. Nailfold capillaroscopy, skin DAS, and muscle DAS assessments
were administered at the first diagnostic outpatient visit (baseline) and every 6 (3) months during a maximum of 36 (6)
months of followup. Nailfold capillaroscopy results and DAS
findings were each graded by the same individuals for each
patient at each time point, without knowledge of the results of
the other assessments. Nailfold capillaroscopy analyses were
performed as previously described (9). The nailfold capillaroscopy images were analyzed for the number of BLs and the total
number of loops (ERLs) per 3-mm section over 8 digits. The
severity of juvenile DM involvement was assessed using the
validated juvenile DM DAS (11). The total DAS (see Appendix A, available on the Arthritis & Rheumatism Web site at
http://www.mrw.interscience.wiley.com/suppmat/0004-3591/
suppmat/) is a 20-point scale with 2 subscales, one for musculoskeletal findings (assessing muscle function and extent of
weakness, with a maximum possible score of 11) and the other
for dermatologic findings (assessing the extent and severity of
rash, presence of Gottrons papules, and/or telangiectasia
[defined as tiny, superficial dilated blood vessels with no
particular pattern] of nailfolds, palate, and/or eyelids, with a
maximum possible score of 9). A higher DAS represents
greater disease activity. Nailfold capillaroscopy was also performed on 33 healthy children as controls, after informed
consent was obtained from legal guardians.
Genotyping. TNF 308 polymorphisms were identified as TNF 308A (AA/AG) or TNF 308G (GG).
HLADQA1*0501 status was determined as previously described (1).
Classification of disease course. Disease course was
classified as unicyclic or non-unicyclic. Unicyclic course was
defined as stable clinical status, with a total DAS remaining at
3 at all assessments during the 36-month observation period.
Our clinical experience suggests that a total DAS of 3 is
associated with clinically inactive, stable disease. Non-unicyclic
course was defined as a disease course showing evidence of
continued clinical activity, with a DAS of 3. In order to verify
the consistency of the definition of unicyclic and non-unicyclic
disease course, a subset of patients was classified based on
5-year followup data. The disease course classification using
3-year and 5-year data was then compared. In the unicyclic
disease course group, most of the children had discontinued all
immunosuppressive therapy before 36 months and had no
recurrence in the 23 years after discontinuation. Those in the
non-unicyclic disease course group were observed to have
disease activity necessitating either continuous or repeated
immunosuppressive therapy for 36 months. This report does
not focus on the type of therapy received by the children (dose,
route, or frequency) since the goal of the study was to identify
the association of the type of disease course with periungual
telangiectasia, regardless of the treatment utilized.
Statistical analysis. Values obtained in children with
untreated juvenile DM were compared with those obtained
after up to 36 months of therapy. Continuous changes were
analyzed using the values collected every 6 months (3
months) for up to 36 months. Repeated-measures linear
regression analysis was used to determine the association
between the primary predictor (DAS) and nailfold capillaroscopy outcomes. Time in the longitudinal model was treated as
a continuous variable. A mixed-effects approach was used to
12 (20)
49 (80)
49 (80)
12 (20)
20 (33)
41 (67)
30 (50)
30 (50)
36 (59)
25 (41)
573
RESULTS
Patient characteristics. Over a 10-year period, 96
children were diagnosed as having untreated juvenile
DM by one of the authors (LMP). Of these, 19 had
received immunosuppressive therapy before their first
nailfold capillaroscopy, 7 had no TNF allele analysis, 2
had overlap syndrome, and 7 had only 1 followup visit.
The remaining 61 patients were included in the study.
The mean SD followup time was 29.6 10.2 months
(range 3.238.6). There were a total of 375 concurrent
nailfold capillaroscopy and DAS observations during the
36-month observation period. Forty-nine patients (80%)
had 5 observations. Followup data were available on
40 patients at 36 months and on 31 patients at 60 months.
Sex, race, disease course, and TNF 308 and HLA
DQA1*0501 allele status are summarized in Table 1.
Disease activity and nailfold capillaroscopy results. At baseline, the 61 patients had a mean SD of
5.63 1.70 ERLs/mm (range 3.1310.29) and 0.13
0.15 BLs/mm (range 00.71), a skin DAS of 5.59 1.45
(range 08), and a muscle DAS of 5.20 2.92 (range
010). At 36 months (n 40), the number of ERLs/mm
was 6.32 1.35 (range 3.139.33), the number of
BLs/mm was 0.15 0.16 (range 071), the skin DAS was
2.63 2.35 (range 07), and the muscle DAS was 0.56
0.88 (range 03). The 25th quartile and 75th quartile
values of the number of ERLs/mm in the 33 healthy
controls were 7.61/mm and 8.94/mm, respectively.
Table 2. Differences in disease features between juvenile DM patients with a unicyclic disease course and those with a non-unicyclic disease
course*
Non-unicyclic disease
course (n 36 at baseline;
n 23 after 36 months
of treatment)
0.05
0.44
0.14
0.78
0.035
0.65
0.007
0.53
0.001
0.025
* Values are the mean SD (range). DM dermatomyositis; DAS juvenile DM Disease Activity Score; ERLs end-row loops; BLs bushy
loops.
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CHRISTEN-ZAECH ET AL
Figure 1. Differences in study parameters between juvenile dermatomyositis (DM) patients with a unicyclic and those with a non-unicyclic disease
course over 36 months of treatment. Patients were untreated at study initiation. A, Regeneration of end-row loops. Shaded area shows the 25th to
75th quartile values in 33 healthy control children. B, Juvenile DM skin Disease Activity Score (DAS). C, Juvenile DM muscle DAS. D, End-row
loop regeneration, skin DAS, and muscle DAS findings at 60-month followup compared with those at 36-month followup, showing relatively little
change between the 2 time points. Values are the mean SD.
575
non-unicyclic disease course may be more useful. Patients with a polycyclic and chronic continuous course
overlap in their clinical features, prognoses, and recommended medical interventions; therefore, in the present
study they were combined into 1 group, called nonunicyclic disease. The definition of a unicyclic disease
course as a total DAS of 3 at all assessments (2
assessments in all cases) during a 36-month period is
both novel and helpful. This definition is new and
empirical and differs from previous uses of the term, in
which patients were classified as having unicyclic disease
if they had 1 episode of juvenile DM symptoms with
permanent remission 2 years after diagnosis and therapy. Further studies are needed to validate this new
definition.
A longer duration of untreated disease was found
to be associated not only with persistent nailfold capillaroscopy abnormalities, but also with a non-unicyclic
disease course. Consistent with previous findings (14),
early, effective therapy was associated with a higher
likelihood of a unicyclic pattern. The inflammatory
disease process itself evolves, and duration of untreated
disease is a critical element in the pathophysiology of the
illness (7). Nailfold capillaroscopy data at diagnosis
cannot be used to predict the course of disease, but if the
vascular abnormalities persist, they provide another
sensitive parameter of chronic disease activity and damage and should prompt the clinician to consider continued and aggressive therapy. Since nailfold capillaroscopy
findings correlated with skin disease activity, the observation of nailfold capillaroscopy abnormalities in the
setting of subtle skin changes is often very useful,
providing insight into the disease process. Our results
indicate that neither TNF 308 nor DQA1*0501 is a
useful marker for predicting the chronicity of the disease
in treated juvenile DM patients, and neither was associated with nailfold capillary changes. Investigators at our
institution previously reported that the TNF 308A
polymorphism was associated with disease chronicity
(5). The present seemingly contradictory results likely
reflect the shift toward more aggressive early therapy at
our center, leading to a milder disease course with
significant reduction in the development of pathologic
calcifications.
In children with treated juvenile DM, a unicyclic
disease course was associated with increased ERL regeneration and improvement in both skin DAS and
muscle DAS at 36 months, which was maintained at 60
months in 81% of patients. The improvement of skin
signs was observed to be a very gradual process, in
parallel with the regeneration of capillary ERLs. The
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CHRISTEN-ZAECH ET AL
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