Longitudinal changes in nailfold videocapillaroscopy findings differ by myositis-specific autoantibody in idiopathic inflammatory myopathy

Abstract

Objective

To assess the longitudinal changes in nailfold videocapillaroscopy (NVC) in patients expressing myositis-specific autoantibodies [anti-aminoacyl-tRNA synthetase (ARS), anti-transcriptional intermediary factor 1 (TIF1), and anti-melanoma differentiation-associated gene 5 (MDA5)].

Methods

This study was performed retrospectively, at a single site, on an observational cohort. Seventy-one idiopathic inflammatory myopathy patients were included (25 patients expressed anti-MDA5 Abs, 24 patients expressed anti-TIF1 Abs, and 22 patients expressed anti-ARS Abs). NVC findings included giant, enlarged, and reduced capillaries, haemorrhages, capillary ramification, disorganization of the vascular array, and capillary loss. NVC findings were compared from baseline to after disease activity stabilization.

Results

The frequency of enlarged capillaries at baseline was different among the three groups, and was significantly higher in patients with anti-TIF1 Abs compared with those with anti-ARS Abs (88% vs 55%, P < 0.05). Reduced capillaries were significantly increased in patients with anti-TIF1 Abs compared with those with anti-MDA5 (96% vs 44%, P < 0.0001) or anti-ARS Abs (96% vs 50%, P < 0.0005). Both enlarged and reduced capillaries improved after stabilization in patients with anti-MDA5 Abs (P < 0.0001 and P < 0.05, respectively). These improvements were not observed in patients expressing anti-TIF1 and anti-ARS Abs. However, a significant reduction in haemorrhages was observed in all three groups (P < 0.0001 for each group).

Conclusions

The results of this study demonstrate that longitudinal changes in NVC findings may vary depending on myositis-specific Ab expression. Therefore, it is crucial to assess individual NVC findings separately, as each finding may impact disease activity in a different manner.

DM, capillaroscopy, nailfold capillary changes

Rheumatology key messages

• Longitudinal changes in NVC findings for each MSA have not yet been elucidated.

• Enlarged and reduced capillaries improved in anti-MDA5 Ab, but not in anti-TIF1 and anti-ARS Abs.

• Longitudinal changes in NVC findings may differ for each MSA.

Introduction

Idiopathic inflammatory myopathy (IIM) is an autoimmune, connective tissue disease, in which characteristic patterns of inflammatory injury occur in striated muscle. Although the pathophysiology of IIM has not been elucidated, nailfold videocapillaroscopy (NVC) abnormalities are characteristic in IIM, and may serve as an indicator of peripheral microangiopathy. NVC is a technique that allows for a non-invasive, real-time assessment of vascular abnormalities [1–3]. The clinical usefulness of NVC has been established by examining the relationship between NVC findings and disease activity in SSc [4], and based on these findings NVC has recently been applied to IIM [5–7]. Mugii et al. reported an association between NVC findings and disease activity in patients with DM [6]. Capillaroscopic alterations, including disorganization of the vascular array, enlarged and giant capillaries, capillary loss and an SSc-like pattern, were more prominent in patients with DM than those with PM [8]. Another study reported that DM and overlap myositis NVC findings differed from antisynthetase syndrome and immune-mediated necrotizing myopathy; the frequency of giant capillaries was higher in overlap myositis than DM, and absent in the other two diseases [7].

A variety of serum autoantibodies (auto Abs), referred to as myositis-specific auto Abs (MSAs), are found in patients with IIM [9, 10]. MSAs include anti-aminoacyl-tRNA synthetase (ARS) Abs, anti-transcriptional intermediary factor 1 (TIF1) Abs, and anti-melanoma differentiation-associated gene 5 (MDA5) Abs. Clinically, it is important to identify the specific MSAs expressed in patients with IIM, because each Ab is closely associated with specific clinical features [11]. Given the observed differences in clinical manifestations, it is of interest to determine whether the pattern of NVC findings also differs by MSA expression. When comparing NVC findings between anti-MDA5 Ab and anti-ARS Ab positive DM patients with interstitial lung disease (ILD), it was found that the median scores of microhaemorrhage and capillary disorganization were higher in the anti-MDA5 Ab positive-group; however, the median scores of tortuous capillaries were higher in the anti-ARS Ab-positive group [12]. These results indicate that the observed NVC findings in DM differ for each MSA.

Previously, a study in SSc patients indicated that NVC findings are chronically progressive and irreversible [13]. Sulli et al. examined the longitudinal changes in NVC findings and reported that 53 out of 90 patients (59%) had worsening NVC findings, while 22 patients (24%) showed an improvement, and 15 patients (17%) exhibited no changes at the time of follow-up [14]. However, longitudinal changes in NVC findings based on MSA expression have not yet been elucidated.

In the present study, we examined the longitudinal changes in NVC findings between patients expressing the anti-MDA5, anti-TIF1 and anti-ARS Abs. NVC findings differed for each MSA when compared at baseline and after disease stabilization by treatment, indicating that MSA differences should be considered when assessing NVC findings for long-term follow-up.

Materials and methods

Patients and clinical parameters

This retrospective study was performed on an observational cohort of patients who visited Kanazawa University Hospital between 1 April 2006 and 31 December 2019. A total of 71 Japanese IIM patients expressing anti-MDA5, anti-TIF1 or anti-ARS Abs [54 females and 17 males, with a median age of 57 years (range 2–82 years)] were included in the study (Table 1). Disease duration was calculated from the first observed manifestation of IIM in the clinic. DM diagnosis was based on the Bohan and Peter criteria for definite or probable diagnosis [15]. The diagnosis of clinically amyopathic DM (CADM) was based on criteria proposed by Sontheimer [16], as follows: clinical skin manifestations typical of DM, with minimal or no clinical features of myositis for >2 years after the onset of skin manifestations. Antisynthetase syndrome (ASS) was diagnosed in patients who were positive for anti-ARS Abs and exhibited one or more of the following clinical features: myositis, interstitial lung disease (ILD), fever, Raynaud’s phenomenon, arthritis and mechanic’s hands.

Table 1

Baseline clinical and laboratory features for 71 Japanese patients with idiopathic inflammatory myopathy

	Anti-MDA5 (n = 25)	Anti-TIF1 (n = 24)	Anti-ARS (n = 22)	Overall P-value	Mutual comparisons among the three MSAs
Age at onset, median (range) years	52 (2–72)	63.5 (15–82)	53 (18–73)	0.3390
No. of females/no. of males	17/8	20/4	17/5	0.4475
Disease duration, median (range) months	2 (0.2–8)	2 (0.4–23)	8 (0.2–36)	<0.0001	P < 0.0001, MDA5 vs ARS; P < 0.005, TIF1 vs ARS
Observation period, median (range) months	27 (6–96)	11.5 (2–87)	18 (5–58)	0.0479	P < 0.05, MDA5 vs TIF1
Diagnosis
Antisynthetase syndrome	0	0	22	<0.0001
Dermatomyositis	9	18	0
Clinically amyopathic DM	16	6	0
Skin eruptions
Heliotrope rash	40	63	14	<0.005	P < 0.005, TIF1 vs ARS
Facial erythema other than heliotrope rash	64	83	14	0.0001	P < 0.005, MDA5 vs ARS; P < 0.0001, TIF1 vs ARS
Gottron’s sign/papules	100	88	41	<0.0001	P < 0.0001, MDA5 vs ARS; P < 0.005, TIF1 vs ARS
Periungual erythema	96	92	41	<0.0001	P < 0.0001, MDA5 vs ARS; P < 0.0001, TIF1 vs ARS
Nailfold capillary changes	96	88	50	<0.0005	P < 0.0001, MDA5 vs ARS; P < 0.05, TIF1 vs ARS
Flagellate erythema	68	79	27	<0.001	P < 0.05, MDA5 vs ARS; P < 0.005, TIF1 vs ARS
Skin ulcers	12	0	0	0.056
Cutaneous calcification	0	0	0	NS
Clinical features
Fever	40	13	32	0.0913
Raynaud’s phenomenon	4	4	23	0.0513
Arthritis	40	17	73	<0.001	P < 0.05, MDA5 vs TIF1; P < 0.0001, TIF1 vs ARS
Interstitial lung disease	100	13	100	<0.0001	P < 0.0001, MDA5 vs TIF1; P < 0.0001, TIF1 vs ARS
Malignancy	4	46	9	<0.0005	P < 0.005, MDA5 vs TIF1; P < 0.05, TIF1 vs ARS
Laboratory findings
CK, IU/L, mean (s.d.)	204 (142)	958 (1948)	3087 (4854)	<0.005	P < 0.005, MDA5 vs ARS; P < 0.05, TIF1 vs ARS
LDH, IU/L, mean (s.d.)	380 (173)	438 (243)	627 (482)	<0.05	P < 0.05, MDA5 vs ARS; P < 0.05, TIF1 vs ARS
KL-6, U/mL, mean (s.d.)	1042 (1030)	364 (279)	1518 (2087)	<0.05	P < 0.005, TIF1 vs ARS
Treatment
Oral corticosteroid	100	92	95	0.3483
Immunosuppressive agents	100	21	68	<0.0001	P < 0.0001, MDA5 vs TIF1; P < 0.005, TIF1 vs ARS

*

Unless otherwise noted, values are percentages of patients. CK: creatine kinase; KL-6: Krebs von den Lungen-6; LDH: lactate dehydrogenase; NS: not significant. CK, LDH and KL-6 levels are reported as the maximum values recorded during the clinical course.

Clinical information was retrospectively collected for all patients through a review of their medical charts. Patients were diagnosed with myositis if one of the following confirmatory examinations showed findings compatible with inflammatory myopathy: a myogenic pattern on an electromyogram [15]; muscular oedema on T2-weighted images with fat suppression on an MRI [17]; necrosis, regeneration, and some atrophy of muscle fibres; or inflammatory cell infiltration in muscle biopsy [15]. Patients were diagnosed as having ILD based on chest images from high-resolution computed tomography. Internal and haematologic malignancies were recorded if malignant disease was diagnosed concurrently with, or within three years of, DM/ASS diagnosis, or if malignant disease occurred three years prior to DM/ASS diagnosis [18]. All 71 patients received treatment for skin, muscle, and/or lung involvement at baseline and their disease activity was stabilized by treatment. Disease activity stabilization was defined as the maintenance of stable clinical symptoms, including muscle involvement, ILD, arthritis, and skin eruptions, with a daily dose of 10 mg or less of an oral corticosteroid for at least six months. All study participants provided written informed consent and the study protocol was approved by Kanazawa University Hospital (No. 963).

MSA detection

Anti-MDA5, anti-TIF1 or anti-ARS Abs were identified using an immunoprecipitation assay [19–21] and/or an enzyme-linked immunosorbent assay (ELISA). Validated ELISA kits were used to detect the anti-MDA5 Ab [22], anti-TIF1 Ab [23] and anti-ARS Ab [24] expression based on the references provided (MBL, Nagoya, Japan).

NVC pattern classification

We assessed NVC findings using the following videocapillaroscopy systems: CP-1000 (Chunichi Denshi, Nagoya, Japan) and/or GOKO Bscan/Bscan-Z (GOKO Imaging Devices, Kawasaki, Japan), as previously reported [6]. We assessed seven abnormal findings: enlarged capillaries; reduced number of capillaries (reduced capillaries); greater than two punctate haemorrhages per finger or confluent haemorrhage areas (haemorrhages); tortuous, crossed, and/or ramified capillaries (capillary ramification); disorganization of normal capillary distribution (disorganization of the vascular array); moderate or extensive capillary loss (loss of capillary); and giant capillaries. In this study of longitudinal changes in NVC findings, we assessed NVC findings at baseline and after stabilization of disease activity.

Statistical analysis

Statistical analyses were performed using JMP 10 Statistical Discovery Software (SAS Institute, Cary, NC, USA). A chi-squared test and a Student’s t-test were used to compare the frequency and the mean value of the percentage of patients with each individual NVC finding. A Spearman’s rank correlation coefficient was used to examine the relationship between two continuous variables and a Bonferroni correction was performed for multiple comparisons. A P-value of <0.05 was considered statistically significant.

Results

Baseline characteristics of IIM patients

The baseline characteristics of the 71 IIM patients in the present study are summarized in Table 1. A totally of 25 patients were anti-MDA5 Ab positive, 24 patients were anti-TIF1 Ab positive and 22 patients were anti-ARS Ab positive. The 22 anti-ARS Ab positive patients consisted of eight patients with anti-Jo-1 Ab, six with anti-EJ Ab, five with anti-PL-7 Ab, and a single case with anti-PL-12, anti-KS and anti-OJ Abs. The age of disease onset and the gender ratio (female/male) were comparable across all three groups. Disease duration was significantly longer in patients expressing the anti-ARS Ab compared with those who expressed either the anti-MDA5 Ab or the anti-TIF1 Ab (P < 0.0001 and P < 0.005, respectively). The observation period was significantly shorter in patients expressing the anti-TIF1 Ab compared with those expressing the anti-MDA5 Ab.

For specific disease diagnoses, it was found that CADM (64%) was predominant in patients expressing the anti-MDA5 Ab and 75% of the patients expressing the anti-TIF1 Ab that were diagnosed with DM. All 22 patients expressing the anti-ARS Ab were diagnosed with ASS. Patients expressing the anti-ARS Ab were found to have an overall lower frequency of skin eruptions when compared with patients expressing either the anti-MDA5 or the anti-TIF1 Abs.

With respect to clinical manifestations, the frequencies of fever and Raynaud’s phenomenon were similar among all three groups. Arthritis and ILD were infrequent in patients expressing the anti-TIF1 Ab, while malignancy was frequently observed. The maximum creatine kinase (CK) and lactate dehydrogenase (LDH) values reported during the clinical course were significantly higher in patients expressing the anti-ARS Ab compared with those expressing either the anti-MDA5 and anti-TIF1 Abs. KL-6 (Krebs von den Lungen-6) levels in patients expressing the anti-ARS Ab were significantly higher when compared with those expressing the anti-TIF1 Ab; while no statistical difference was observed when compared with patients expressing the anti-MDA5.

Nearly all of the patients enrolled in the present study received an oral corticosteroid treatment regardless of the auto Ab type. However, the number of patients receiving immunosuppressive agents was smaller in the anti-TIF1 Ab positive group. The demographic and clinical features observed in the study patients were generally consistent with the previously reported characteristics for each auto Ab.

NVC findings at the baseline assessment

First, we compared the frequencies of each NVC finding at the initial baseline visit for all 71 patients, classified according to the presence of three MSAs (Table 2). NVC findings were comparable between patients with anti-Jo-1 Ab and those with non-anti-Jo-1 Ab (Supplementary Table S1, available at Rheumatology online). Enlarged capillaries were observed in 18 of the 25 patients (72%) expressing the anti-MDA5 Ab, 21 of the 24 patients (88%) expressing the anti-TIF1 Ab and 12 of the 22 patients (55%) expressing anti-ARS Ab. The frequency was significantly different among the three groups, and was significantly higher in patients expressing the anti-TIF1 Ab than in those expressing the anti-ARS Ab (P < 0.05). Reduced capillaries were identified in significantly more patients expressing the anti-TIF1 Ab compared with those expressing the anti-MDA5 (44% vs 96%, P < 0.0001) or the anti-ARS Ab (50% vs 96%, P < 0.0005). No significant difference was observed between the three groups regarding the number of patients with reported haemorrhages, disorganization of the vascular array, capillary loss and giant capillaries. In all three groups, >80% of patients had haemorrhages; however, instances of disorganization of the vascular array, capillary loss and giant capillaries were rare.

Table 2

Baseline findings of nailfold videocapillaroscopy in 71 Japanese patients with idiopathic inflammatory myopathy

	Anti-MDA5 (n = 25)	Anti-TIF1 (n = 24)	Anti-ARS (n = 22)	Overall P-value	Mutual comparisons among the three MSAs
Enlarged capillaries	72% (18)	88% (21)	55% (12)	0.0459	P < 0.05, TIF1 vs ARS
Reduced capillaries	44% (11)	96% (23)	50% (11)	0.0002	P < 0.0001, MDA5 vs TIF1; P < 0.0005, TIF1 vs ARS
Haemorrhages	92% (23)	92% (22)	82% (18)	0.4664
Capillary ramifications	0% (0)	4% (1)	9% (2)	0.3027
Disorganization of the vascular array	12% (3)	13% (3)	14% (3)	0.9854
Loss of capillary	4% (1)	0% (0)	5% (1)	0.5875
Giant capillaries	4% (1)	0% (0)	0% (0)	0.3933

Changes in NVC findings across the longitudinal study

All patients who were diagnosed with active DM/ASS at the baseline visit were followed until the disease was stabilized through treatment with immunosuppressive agents. All of the clinical parameters reflecting disease activity were improved by treatment (Supplementary Table S2, available at Rheumatology online). The presence of enlarged capillaries disappeared after stabilization in patients expressing the anti-MDA5 Ab (P < 0.0001) (Figure 1A); however, this did not occur in patients expressing the other two Abs. Additionally, the frequency of reduced capillaries was also significantly decreased only in patients expressing the anti-MDA5 Ab (P < 0.05) (Figure 1B). The number of patients who had haemorrhages was significantly reduced in all three groups (P < 0.0001, respectively, Figure 1C). Both capillary ramifications and disorganization of the vascular array were increased after treatment in all three groups; however, a significant difference was observed only in the anti-MDA5 Ab-positive group for capillary ramifications (Figure 1D and 1E). Capillary loss and giant capillaries were not seen in most patients from any of the three groups (Figure 1F and 1G). These results demonstrate that changes in NVC findings over the course of clinical care differed among the three groups. While haemorrhages disappeared in all three groups, both enlarged and reduced capillaries only improved in patients expressing the anit-MDA5 Ab.

Fig. 1

Frequencies of nailfold videocapillaroscopy findings

Frequencies of nailfold videocapillaroscopy findings in patients expressing either the anti-MDA5, the anti-TIF1 or the anti-ARS antibody, before treatment (B) and after stabilization (A). Frequencies are reported as the percentage of patients with each individual finding and are depicted in the following panels: (A) enlarged capillaries; (B) reduced capillaries; (C) haemorrhages; (D) capillary ramifications; (E) disorganization of the vascular array; (F) loss of capillary; and (G) giant capillaries.

Additionally, we examined the association between NVC pattern changes and clinical parameters including MSA titre. In patients expressing the anti-MDA5 Ab, enlarged capillaries and haemorrhages were associated with an improvement in clinical parameters including anti-MDA5 Ab titre. Conversely, in patients expressing the anti-TIF1 and anti-ARS Abs, haemorrhages were associated with an improvement in clinical parameters, but enlarged capillaries and reduced capillaries were not. With regard to MSA titre, a decrease of anti-TIF1 Ab titre was associated with a disappearance of haemorrhages, but not associated with enlarged and reduced capillaries. We could not evaluate an association between the anti-ARS Ab titre and NVC findings, as only two patients expressing the anti-ARS Ab had their titre measured over time.

NVC pattern changes before and after treatment

Representative images depicting NVC changes before and after treatment for each MSA are shown in Fig. 2. The first panel shows images from a patient expressing the anti-MDA5 Ab. Enlarged capillaries, multiple haemorrhages and reduced capillaries were present prior to treatment (at the baseline visit). However, after treatment (at stabilization), the enlarged capillaries disappeared, and multiple haemorrhages and the reduced capillaries were almost completely restored to normal conditions with nascent capillary ramifications (Fig. 2). In contrast, the next two panels demonstrate that there were no changes to the enlarged and reduced capillaries after stabilization of disease activity in patients expressing the anti-TIF1 anti-ARS Abs. However, haemorrhages were reduced in these patients.

Fig. 2

Representative images of nailfold videocapillaroscopy findings

Representative images of nailfold videocapillaroscopy findings in patients expressing the anti-MDA5, anti-TIF1 and anti-ARS antibodies at baseline and after stabilization.

Discussion

This study is the first to examine the long-term changes to NVC findings in IIM patients expressing the anti-MDA5, anti-TIF1 and anti-ARS Abs from a baseline visit to stabilization after treatment. At the baseline visit, NVC findings differed among the three groups; enlarged capillaries were less frequent in patients expressing the anti-ARS Ab, while reduced capillaries were more common in patients expressing the anti-TIF1 Ab, and haemorrhages were frequently observed in all three groups. With regard to NVC changes at the long-term follow-up timepoint, this study demonstrated that both enlarged and reduced capillaries improved after disease stabilization in patients expressing the anti-MDA5 Ab; however, this was not true for patients expressing the anti-TIF1 and anti-ARS Abs. The frequency of haemorrhages was significantly decreased in all three groups. Therefore, while the observed NVC findings were generally consistent with overall DM/ASS activity, the differences noted in this study suggest that it is necessary to consider the fact that NVC findings may differ by MSA expression in patients through the course of clinical care.

The clinical significance and usefulness of NVC findings has been extensively examined in SSc. In recent years, the number of studies investigating NVC findings in IIM has been increasing. The totality of the data gathered from patients with IIM has revealed both differences and similarities in the clinical significance and usefulness of NVC findings compared with SSc.

While there have not been many reports examining NVC findings based on MSA expression, previous reports indicate that each MSA may have their own characteristics. In a study of 190 patients that expressed the anti-ARS Ab, NVC findings were observed in 62% of patients and an SSc-like pattern was detected in 35% of patients. The study determined that the SSc-like pattern was associated with the expression of the anti-Jo-1 Ab [25]. Another study demonstrated that anti-Jo-1 Ab positivity did not influence the scores of the main capillary parameters [26]. Kubo et al. reported that the prevalence of NVC findings was significantly higher in IIM patients expressing the anti-MDA5 Ab (87.5%) and the anti-TIF1γ Ab (88.9%) compared with those expressing anti-ARS Ab (26.9%) [27]. These results are consistent with the present study in which the frequency of enlarged capillaries was the lowest in patients expressing the anti-ARS Ab and the presence of reduced capillaries was the highest in patients expressing the anti-TIF1 Ab. Haemorrhages were observed in most of the patients from all three groups. Therefore, MSA subtypes should be considered when assessing NVC findings.

A novel finding of the present study is the demonstration that the long-term course of NVC findings in IIM patients differs for each MSA. Previous studies in SSc have indicated that NVC findings are chronically progressive and irreversible [13, 28]. In contrast, there are several reports describing that NVC findings are reversible and associated with disease activity in patients with IIM [6, 27, 29]. A reduction in the scores for enlarged capillaries, haemorrhages and capillary loss has been observed in patients after stabilization of disease activity through treatment [6]. It has also been shown that NVC findings disappeared in 75% of IIM patients one year after immunosuppressive therapy, in contrast to the stability of NVC findings observed in SSc patients [27]. In DM patients, NVC findings were reversible by treatment, and serum FGF23 levels reflected the degree of microvascular damage in patients expressing the anti-MDA5 Ab [29]. However, another study showed no statistically significant variation in capillaroscopic scores at a three-year follow-up visit [26]. In the present study, while haemorrhages were improved for all three groups, enlarged and reduced capillaries were only significantly improved in patients expressing the anti-MDA5 Ab. Therefore, although NVC findings reflect IIM disease activity, the assessment should also take into account the MSA subtype. Furthermore, while vascular damage is one of the key pathophysiological features of IIM, its role may vary in patients expressing different MSAs. Recently, it was suggested that anti-MDA5 and TIF1-γ Ab levels can be useful and relevant surrogate markers for disease activity [30, 31]. The present study confirmed that NVC findings can be an effective surrogate marker of disease activity; however, it should be recognized that individual NVC findings may have different clinical significance based on MSA expression.

When assessing NVC findings in patients with IIM, the term ‘SSc-like pattern’ is often used. An SSc-like pattern is defined as an alteration of the nailfold microvascular network, characterized by enlarged and giant loops, microhaemorrhages, capillary loss, ramified capillaries and architectural disorganization [13, 14, 28]. Sebastiani et al. chose to use the term referring to an NVC pattern similar to the SSc-like pattern when evaluating NVC findings in patients with ASS [25]. We have previously defined an SSc-like pattern with modifications according to Bergman et al. [6, 32] as follows; a pattern containing two or more of the following abnormalities: enlarged capillaries, haemorrhages (more than two punctate haemorrhages per finger, or confluent haemorrhage areas), disorganization of normal capillary distribution, moderate or extensive capillary loss (i.e. avascular areas), and tortuous, crossed and/or ramified capillaries. The term SSc-like pattern is practical and useful in the clinical field. Yet when assessing NVC findings in patients with IIM, it may be better to evaluate NVC findings separately, rather than collectively as an SSc-like pattern, given that the clinical significance of each NVC finding may vary by MSA expression.

The present study examined NVC findings in patients expressing the anti-MDA5, anti-TIF1, and anti-ARS Abs. Differences in NVC findings for patients expressing other MSAs, including anti-Mi-2, anti-NXP-2, anti-SRP and anti-SAE Abs, or Abs without MSA, have yet to be elucidated. The findings in this study demonstrate that it is clinically relevant to examine NVC findings for each anti-ARS Ab. Thus, it is necessary to accumulate relevant data to address this issue.

There are several limitations to the present study. This study was performed retrospectively; thus, a prospective study is needed to confirm the study results. Additionally, this study was limited in sample size and included only Japanese patients, which limits generalizations that can be gleaned from the findings. Also, the observational period for patients expressing the anti-TIF1 Ab was significantly shorter than for patients expressing the other two Abs. This may have affected the analysis of NVC abnormalities in these patients and may be a reason sufficient improvement was not observed for some findings. Moreover, treatment intensity or the level of disease activity during the maintenance phase may have differed among the patients expressing the three MSAs examined, which may have influenced the NVC findings. In addition, it is possible that temperature or other seasonal effects, which were not assessed in this study, may have affected the results. Future studies, accounting for these issues, and including an increased number of patients and different ethnicities, are necessary to confirm the findings of the present study.

In conclusion, it is important to consider that changes in NVC findings over the course of time from baseline diagnosis to disease stabilization may differ for each MSA. Thus, it may also be necessary to assess each NVC finding individually in IIM.

Funding: No specific funding was received from any bodies in the public, commercial or not-for-profit sectors to carry out the work described in this article.

Disclosure statement: The authors have declared no conflicts of interest.

Data availability statement

The data underlying this article will be shared on reasonable request to the corresponding author.

Supplementary data

Supplementary data are available at Rheumatology online.