MethodsPatient population

Untreated JDM (n = 140), who met diagnosis of JDM [6], and 1:3 ratio of age, sex, race matched healthy controls (n = 46) gave written, age-appropriate informed consent (Ann & Robert H. Lurie Children’s Hospital of Chicago IRB# 2010–14117, 2001–11715, 2011–14651) (Table 1). Written informed consent was obtained from all legally authorized representatives and assent from those patients aged 12 and older. The children with JDM were diagnosed and seen at Lurie Children’s between 1993 and 2021, and had proximal muscle weakness, the characteristic rash, varying degrees of elevated muscle enzymes and, since 2000, a T2 weighted MRI image of involved muscle. Children with overlap syndrome (positive anti-U1 RNP, anti-U2 RNP or anti-PM-Scl), Systemic Lupus or Scleroderma were excluded.

Table 1 Demographics of untreated JDM and healthy controlsClinical assessments

Routine clinical laboratory tests were performed in the Lurie Children’s diagnostic laboratories, while The Oklahoma Medical Research Foundation assayed the Myositis Specific Antibodies (MSA), using immune precipitation and immunodiffusion [7]. Their early MSA data were first available after 2002, and the P155/140 (Tif-1-γ), MJ (NXP-2), and MDA5 (anti-CADM140) antibodies were reported after 2012. Of the 140 untreated JDM in this study, 94 had current MSAs, including these newly reported antibodies. The Disease Activity Score (DAS) was obtained by a pediatric rheumatologist; DAS-total score (DAS-T) (range = 0–20), is derived by adding the muscle evaluation (DAS-M) (range = 0–11) to the skin score (DAS-S) (range = 0–9) [8]. A physical therapist obtained The Childhood Muscle Assessment Scale (CMAS) [9]. The duration of untreated disease (DUD) is defined as the length of time that the parents/caregiver first noted either new physical signs of JDM or change in activity to the date of the first JDM treatment.

Nailfold capillaroscopy

Since 2012, a digital camera (Nikon Coolpix p6000) equipped with a Dermlite2 ProHR provided standardized NFC images (18x) to generate the data and assess inter-rater reliability, prior to 2012, freeze frame videomicroscopy was utilitized as previously described [5]. Figure 2 illustrates the difference seen in healthy control and untreated JDM periungual NFCs. Qualitative measures, such as severity of avascularity, and predominant ERL shape are entered on the NFC work sheet (Table 2). The main patterns of ERLs are open, undefined, crossed, bushy, branched, and tortuous; the predominant pattern was recorded, Fig. 3. The reproducibility of the method was assessed by two experienced readers who analyzed the images of 49 JDM utilizing Photoshop –see accompanying 3-min video of the method (attachment).

Table 2 Assessment score sheet for ERL in children with JDM and their controlsStatistical analysis

The association of a panel of JDM clinical factors with the NFC data was assessed using Pearson’s correlation co-efficient, correcting for number of comparisons made utilizing the Bonferonni correction. Standard t-tests were employed on other occasions. The association of the shape of the nailfold capillary ERL with the child’s MSA was determined by Chi-square analysis. The statistics were performed in SPSS and figures were generated using Graphpad Prism 9 software.

ResultsInter-rater reliability for NFC analysis

Two trained observers, assessing nailfold data from 49 children with JDM were highly correlated for ERL/mm counts (r = 0.817, p =  < 0.0001).

NFC studies of 140 untreated JDM and 46 matched healthy controls

In general, the JDM patients had moderate disease activity at the time of their first nailfold photography; the mean DAS-T = 10.8 ± 3.3 SD; (DAS-S = 5.7 ± 1.3; DAS-M = 5.1 ± 2.8); the von Willebrand Factor Antigen (vWF:Ag) (corrected for blood group antigen) was elevated in 24% (mean 159.6 ± 88.0%) of untreated JDM (Table 3). JDM patients had fewer ERLs than healthy controls (5.1 ± 1.5/mm vs 7.9 ± 0.9/mm, p < 0.0001, Table 1, Fig. 4a). Neither group had a significant association of ERL density with sex (JDM: p = 0.277, healthy control: p = 0.98) or age (JDM: r = 0.096, p = 0.99, healthy control: r = -0.211, p = 0.16). The longer the duration of untreated disease, the more damage to the ERL: (r = -0.174, p = 0.28). For the entire untreated JDM group, the children with decreased ERL had more skin symptoms than muscle findings (DAS-S: r = -0.267, p = 0.014 vs DAS-M: r = 0.032, p = 0.99).

Table 3 Correlations of clinical factors and end row capillary loops in untreated JDMFig. 4

a Nailfold capillary end row loop (ERL) density in 140 untreated children with JDM and 46 healthy controls. The dotted line is the mean ± 2 standard deviations (shaded area) for controls. The mean ERL for JDM was 5.0 ± 1.5/mm, vs the mean ERL for healthy controls, 8.0 ± 0.9/mm, p < 0.0001. b The association of a range of MSA with nailfold end row loop capillary density in 94 untreated children with JDM. c Comparison of nailfold end row loop capillary density for 51 untreated children with JDM positive for P155/140 MSA with 43 untreated JDM positive for other MSA or MSA negative, * = significance at 0.05. d The lack of association of a positive antinuclear antibody with a significant difference in the density of the nailfold capillary end row loops

With respect to the MSAs, 44.7% of the children had anti-P155/140 (anti-TIF1-γ), 9.6% anti-Mi2, 9.6% multiple MSA [anti-P155/140 (anti-TIF1-γ), anti-Mi2], 7.4% anti-MJ (anti-NXP-2), 4.3% anti-MDA5 (anti-CADM140), and 24.5% MSA negative JDM, Fig. 4b. P155/140 (anti-TIF-1-γ) was associated with lower ERL density. MJ (NXP-2) antibody was associated with a wider, but still abnormal data range (Fig. 3b). When the anti-P155/140 (anti-Tif-1-γ) group (including children who tested positive for both anti-P155/140 and anti-Mi2) were compared with the aggregated data for the other JDM MSA types, the difference was significant (p = 0. 037), Fig. 4c. The ERL were not associated with a positive anti-nuclear antibody, Fig. 4d.

This study was initiated approximately 25 years before information about the specificity of the MSAs were identified [10]; 33% of the early cases of JDM in this study did not have current MSA data. Assessment of 92 JDM with both current MSA and ERL pattern data disclosed that their initial patterns were: 41% open, 38% undefined, 12% crossed, 7% bushy, and 2% tortuous (Fig. 5a). When the JDM were grouped by their MSAs, those with P155/140 had a predominant ERL pattern that was more “open” than the patterns in the other groups– MSA negative, MSA Mi-2 combined with P155/140, and all other MSA (p = 0.03). As Fig. 5b presents, the undefined pattern was associated with the shorter DUD, with a median of 3.6 months in comparison to those with a crossed shape (median of 10.6 months) or an open shape (median 5.8 months), (Kuskal-Wallis test, p = 0.036). The undefined pattern was also associated with the highest ERL capillary density with a median of 5.6/mm in comparison to 3.8/mm for the crossed group and 4.2/mm for the open group (Kruskal–Wallis test, p = 0.002). Furthermore, when DUD was dichotomized into either a short (≤ 3 months) and long (> 3 months) duration, those children having a shorter DUD had more undefined predominant NFC pattern than those with a longer untreated disease duration (p =  < 0.0001), suggesting progression over time, Fig. 5b. Of note, 13% of the study group had periungual hemorrhages on their first nailfold assessment, which were closely associated with the symptoms of dysphagia (Chi-Square, p = 0.004) (Fig. 5c).

Fig. 5

a Distribution of predominant ERL pattern in untreated JDM patients by various MSAs b Untreated children with short DUD have more undefined patterns than long DUD group (Chi-square, p =  < 0.0001). c Untreated children presenting with dysphagia have more periungual hemorrhages present in their nailfold capillaries than those not presenting with dysphagia (Chi-square, p = 0.004)