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Nailfold capillary abnormalities and clinical outcome in childhood dermatomyositis.

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954
NAILFOLD CAPILLARY ABNORMALITIES
AND CLINICAL OUTCOME IN
CHILDHOOD DERMATOMYOSITIS
GEORGE SPENCER-GREEN, WILLIAM E. CROWE, and JOSEPH E. LEVINSON
The nailfold capillary pattern was observed in a
population of patients with childhood dermatomyositis.
Distinctive nailfold capillary loop abnormalities were
found in 11 of 19 childhood dermatomyositis patients
and in none of 2 control populations (P< 0.001). By a
retrospective analysis of the childhood dermatomyositis
patients, we found that the presence of nailfold capillary
abnormalities correlates with more severe forms of the
disease (ulcerative and chronic types), as opposed to
limited type of disease. These changes occurred independently of disease activity or of cutaneous abnormalities.
Childhood dermatomyositis (CDM) is an inflammatory muscle disease with variable clinical manifestations and an unpredictable course (1-3). The
hallmark of disease expression is proximal muscle
weakness and characteristic rash, although ischemic
ulcerations of the gastrointestinal tract and skin are
often concomitant features. The clinical course can
vary from a short, self-limited episode of muscle
From the Division of Immunology, Departments of Medicine and Pediatrics, University of Cincinnati Medical Center, Cincinnati, OH.
Supported in part by General Clinical Research Grant RR0068- 18, by Clinical Associate Physician Program GCRC-RR-006818-S1, and GCRC Clinfo Grant RR-0068-18-S2, by PHS ARAMIS
Grant PR2125, and by the Southwest Ohio Chapter of the Arthritis
Foundation Scleroderma Fund.
George Spencer-Green, MD: Assistant Professor of Medicine; William E. Crowe, MD: Assistant Professor of Medicine and
Pediatrics; Joseph E. Levinson, MD: Professor of Medicine and
Pediatrics .
Address reprint requests to George Spencer-Green, MD,
Division of Immunology, Department of Medicine, University of
Cincinnati Medical Center, 231 Bethesda Avenue, Cincinnati, OH
45267.
Submitted for publication July 20, 1981; accepted in revised
form January 20, 1982.
Arthritis and Rheumatism, Vol. 25, No. 8 (August 1982)
weakness to severe illness that results in significant
morbidity and, in some cases, death. Management of
CDM is complicated by our inability to predict at
disease onset which course patients will follow. Early
in the disease course, patients with self-limited outcome may have the same clinical and laboratory
parameters as patients who will progress to develop
systemic complications and persistent or progressive
weakness.
Distinctive nailfold capillary abnormalities have
been described in other connective tissue disorders,
primarily in adult populations; these disorders have
included progressive systemic sclerosis (PSS), mixed
connective tissue disease, and adult dermatomyositis
(4-7). These vascular abnormalities have been correlated with the extent of systemic involvement in PSS
and adult dermatomyositis, and they may play a role in
the prospective evaluation of patients with Raynaud’s
phenomenon and mixed connective tissue disease (8).
While previous investigators have noted nailfold capillary abnormalities in dermatomyositis ( 5 ) , these
changes have been described primarily in adults, and a
systematic study of their prevalence in the childhood
form of the disease has not been performed. In this
paper, we describe the nailfold capillary changes in a
population of CDM subjects and suggest a correlation
of these changes with clinical disease type.
PATIENTS AND METHODS
Study group. Nineteen CDM patients who were
actively followed at the Children’s Hospital Medical Center
(CHMC), the Special Treatment Center (STC) for Juvenile
Arthritis at CHMC, and the Division of Immunology of the
University of Cincinnati were studied for 3 months. There
were 6 males and 13 females. The patients’ ages at the time
of our study ranged from 7 to 32 (average 20) years of age,
NAILFOLD CAPILLARY ABNORMALITIES IN CDM
and age at onset of disease ranged from 2 to 21 (average 9.6)
years. At time of diagnosis each had the characteristic rash,
proximal muscle weakness, elevation of at least 1 muscle
enzyme, and/or electromyelogram results typical of inflammatory myopathy. Specimens for muscle biopsies were
obtained in 17 patients, and changes typical of the childhood
form of dermatomyositis were revealed in the results of all 17
biopsies (1). Other diseases were excluded at the time of
diagnosis.
Disease activity at the time of capillaroscopy was
determined by 1 observer (WEC), who did not have knowledge of capillary pattern. Based on a combination of clinical
and laboratory parameters, each patient was judged to have
either active or inactive disease. Those with elevation of
either creatine kinase or aldolase or with progressive objective weakness were considered to have active disease.
Patients with normal muscle enzymes and unchanging or
improving muscle strength on physical exam were considered to have inactive disease.
At the time of examination, the presence or absence
of erythema, hypopigmentation, cutaneous ulcers, or thinning of the skin over the hands was noted.
Clinical outcome groups. Before capillaroscopy , and
independently of the observer (GSG), CDM patients had
been divided into 3 mutually exclusive course types:
955
Limited type. The 6 patients in this subset had
disease that was restricted to muscle weakness and rash,
responded well to steroid therapy, and resolved within I
year, without musculoskeletal residua, calcinosis, or relapse. In this group were 4 females and 2 males; average age
at onset was 11.3 years; and mean disease duration at the
time of examination was 7 years.
Ulcerative type. The 5 patients in this subset had
ulceration of the skin or gastrointestinal tract at some time
during the course of their disease. All but 1 was left with
significant weakness, limitation of motion, or calcinosis.
This group included 4 females and 1 male; the average age at
disease onset was 7.1 years, and mean disease duration at
the time of examination was 9.8 years.
Chronic type. The 8 patients in this outcome group
had severe residual weakness, limitation of motion, or
calcinosis. They differed from the patients with the ulcerative form in that neither gastrointestinal nor cutaneous
ulcerations had occurred. Five females and 3 males were in
this group; the average age at disease onset was 10 years,
and mean disease duration at the time of examination was
12.5 years.
Controls. Two control populations were also studied.
These included: juvenile rheumatoid arthritis (JRA) and
healthy volunteers. The JRA group consisted of 20 JRA
Figure 1. Normal pattern of nailfold capillaries with homogeneous distribution and uniform morphology of vessels (original magnification
x 17).
956
patients (14 female patients and 6 male patients) who were
actively followed at the STC. Age at time of study ranged
from 5 to 27 (average 11.9) years. The group of healthy
volunteers consisted of 20 elementary and secondary school
students (10 boys and 10 girls) with no known illness. Age at
time of study ranged from 7 to 17 (average 10.1) years.
Nailfold capillaroscopy. Observations and photography of skin capillaries were performed by in vivo widefield
capillaroscopy, using minor modifications of techniques
previously described (5). Briefly, a small amount of immersion oil was placed on the skin, and using tungsten illumination and a Zeiss stereo microscope at 25 x or 40 x magnification, we noted the capillary pattern for each subject. Four
standard sites at the nailfold and dorsum of the distal
phalanx of the second and third fingers of both hands were
examined. Using an Olympus SLR camera, 50-mm macrolens, and bellows, a photographic record of each site examined was made for subsequent analysis; these were later
reviewed in a coded fashion in an effort to minimize observer
bias. Data analysis was based on the original stereomicroscopic observations, all of which were performed by one
observer (GSG).
Capillary pattern for each subject studied was judged
to be either normal or abnormal. A normal capillary pattern
consisted of uniform distribution and morphology of capillary loops (Figure I ) . Specifically, there were no areas of
capillary loop dropout or of avascularity, and capillary
morphology was that of homogeneous loops. In marked
contrast was the abnormal capillary pattern in which en-
SPENCER-GREEN ET AL
larged dilated capillary loops were noted, surrounded most
often by a dropout of normal capillary population (Figure 2 ) .
Occasionally seen in conjunction with these dilated capillary
loops were highly tortuous arborized capillary loop clusters,
which were also surrounded by dropout of normal capillary
loops (Figure 3). If capillary abnormalities were noted in any
of the 4 observation sites, the subject’s capillary pattern was
considered abnormal, although, in general, if changes were
present at 1 site, they were present at all 4.
RESULTS
Abnormal nailfold capillary pattern was noted
in 11 of 19 CDM subjects and in none of the 20 healthy
controls or 20 JRA children. In Figure 4, distribution
of capillary changes among the study and control
groups is shown; it is a distribution significantly different than that expected by chance (x2 = 25.6, P <
0.001). Those with the chronic type of CDM most
consistently had capillary changes; 7 of 8 in the subset
had abnormalities. The only patient in this group with
normal capillaries was a 10-year-old boy whose disease began at age 5, characterized at that time by rash
and muscle weakness and only a mild response to
corticosteroid therapy. His course has been characterized by persistent muscle weakness, synovitis, and
Figure 2. Abnormal pattern with dilatation of isolated loops and dropout of surrounding loops (original magnification x 17).
NAILFOLD CAPILLARY ABNORMALITIES IN CDM
957
Figure 3. Detail of arborized clusters of capillary loops surrounded by avascular areas (original magnification x26).
recent conversion of the results of his fluorescent
antinuclear antibody test from negative to positive.
Of 5 patients with ulcerative type of disease, 3
had capillary abnormalities. The 2 with ulcerative
outcome and normal capillaries had the onset of their
N-7
O W
CharTyps
Figure 4. Distribution of nailfold capillary pattern in control and
study groups. CDM = childhood dermatomyositis.
diseases at ages 4 and 6, and the disease of each has
been in remission for over 10 years.
Only 1 of 6 patients with limited-type CDM had
abnormal capillaries. This was an 1 1-year-old boy with
disease onset at age 5 , whose disease had been in
remission for several years. Since our initial observations, he has subsequently developed signs and symptoms of disease activity with recent onset of muscle
weakness and elevated muscle enzymes. Thus, while
he fulfilled our criteria for limited disease at the time of
study, subsequent observation has shown him to have
chronic disease.
At the time of examination, 7 patients had
active and 12 had inactive disease. Of those with
active disease, 2 had normal and 5 had abnormal
capillary pattern, while of the 12 with inactive disease,
6 had normal and 6 abnormal pattern. The correlation
of capillary changes with disease activity is not statistically significant.
Six of 19 CDM patients had skin lesions at the
time of examination; 4 of these patients had chronic, 1
ulcerative, and 1 limited disease. Five of the 6 had
SPENCER-GREEN ET AL
958
abnormal capillary pattern. Of the 13 with no skin
lesions, 6 had abnormal and 7 normal capillary pattern.
The correlation of capillary pattern with the presence
of skin lesions is not statistically significant.
Coded photomicrographs of all subjects were
reviewed by the initial observer (GSG) and a trained
observer (WEC). Technically acceptable photographs
were available for 55 subjects, and concordance of
observed capillary pattern between initial observations and coded slides was found in all 55 subjects by
the initial observer. Between the initial observer and
trained observer, there was agreement of capillary
pattern from coded slides in 53 of 55 subjects.
DISCUSSION
In this study, distinctive nailfold capillary abnormalities were seen in 58% of 19 CDM patients: they
occurred most often in those probands with more
chronic and severe disease types. The interpretation of
these findings is limited by both the small numbers of
subjects in the study as well as its retrospective
design. Additionally, capillaroscopy was not performed at a uniform time in the patient’s course, and,
in some cases, this amounted to more than 10 years
after disease onset. In the limited studies we have
undertaken, however, modulation of capillary pattern
has not occurred with time.
It remains to be established at what point in the
disease course nailfold capillary changes do occur. In
preliminary studies in patients with Raynaud’s phenomenon, researchers have suggested that these
changes might represent an early identifiable marker
of scleroderma (8). However, prospective controlled
studies in diseases in which these changes have been
described are lacking, and so this point remains a
matter of speculation. If it could be established that
nailfold capillary abnormalities occur early in the
disease course of CDM, they might serve as a prognostic marker for disease subset and/or outcome.
Morphologically, the nailfold changes we have
described are similar to those previously described in
PSS, adult dermatomyositis, and mixed connective
tissue disease. In view of these observations, we might
speculate that the pathogenic process responsible for
capillary loop changes in CDM is similar to that seen in
other diseases in which these markers are also present
and that they may represent comparable host response
to an as yet unidentified stimulus. Capillary endothelia1 swelling by electron microscopy has been consistently noted in the muscle bed of patients with PSS (9),
and similar changes were seen in all of 8 subjects in
this study for whom muscle biopsy material was
available for electron microscopic analysis. Additionally, in our earlier studies, we have shown that the
presence of specific vascular lesions iu the muscle bed
of CDM patients, including nonnecrotizing vasculitis,
noninflammatory endarteropathy , and muscle infarction, occur predominantly in patients with capillary
abnormalities (10).
In view of our results, it seems that in CDM,
nailfold capillary abnormalities may potentially be a
marker in patients with more persistent forms of the
disease. If results of future prospective studies confirm
these preliminary observations and if it can be established that these changes occur near disease onset,
nailfold capillaroscopy may be useful in early identification of patients at risk for developing more chronic
forms of the disease and may become an additional
tool to help guide therapy in childhood dermatomyositis.
REFERENCES
1 . Crowe WE, Bove KE, Levinson JE, Hilton PK: Clinical
and pathogenetic implications of histopathology in childhood dermatomyositis. Arthritis Rheum 25: 126-139,
1982
2. Pachman LM, Cooke N: Juvenile dermatomyositis: a
clinical and immunologic study. J Pediatr 96:226-234,
I980
3. Banker B, Victor M: Dermatomyositis (systemic angiopathy) of childhood. Medicine 45:261-285, 1966
4. Maricq HR, Spencer-Green G, LeRoy EC: Skin capillary abnormalities as indicators of organ involvement in
scleroderma (systemic sclerosis), Raynaud’s syndrome
and dermatomyositis. Am J Med 61:862-870, 1976
5 . Maricq HR, LeRoy EC: Patterns of finger capillary
abnormalities in connective tissue disease by “widefield” microscopy. Arthritis Rheum 16:619-628, 1973
6. Maricq HR, LeRoy EC, D’Angelo WA. Medsger TA,
Dogman GP, Sharp GC, Wolfe JF: Diagnostic potential
of in vivo capillary microscopy in scleroderma and
related disorders. Arthritis Rheum 23: 183-189, 1980
7. Redisch W, Messina EJ, Hughes G, McEwan C: Capillaroscopic observations in rheumatic diseases. Ann
Rheum Dis 29:244-253, 1970
8. Maricq HR, Weinberger AB, LeRoy EC: Predictive
value of capillary microscopy in patients with Raynaud’s
phenomenon (abstract). Arthritis Rheum 23:716, 1980
9. Norton WL, Hurd ER, Lewis DC, Ziff M: Evideoce of
microvascular injury in scleroderma and systemic lupus
erythematosus: quantitative study of the microvascular
bed. J Lab Clin Med 71:919-933, 1968
10. Spencer-Green G, Crowe WE, Bove KE, Levinson JE:
Correlation of muscle angiopathy with nailfold capillary
abnormalities in childhood dermatomyositis. Bib1 Anat
20:702-707, 1981
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