Idiopathic inflammatory myopathies (IIM) are a heterogeneous group of autoimmune disorders classically characterized by proximal skeletal muscle inflammation leading to weakness, but they often possess additional systemic manifestations such as cutaneous, pulmonary, and articular disease.1 Although originally dichotomized as either dermatomyositis (DM) or polymyositis, the discovery of new myositis-specific antibodies (MSA) and myositis-associated antibodies has led to the delineation of more refined IIM patient subgroups. The antimelanoma differentiation-associated gene 5 (MDA5) MSA is an example, found to define a clinically distinct DM subgroup characterized by hypomyopathic or amyopathic muscle disease, distinct cutaneous features, and increased risk for rapidly progressive interstitial lung disease (RP-ILD).1,2

Many of the cutaneous manifestations of anti-MDA5 antibody–positive DM (anti-MDA5-DM) are unique or atypical when compared to other IIM subtypes. This can have implications for diagnosis and treatment delays. Atypical features include cutaneous ulceration (with a predilection for the nailfolds and overlying Gottron papules/sign), palmar papules (occurring on the palms and palmar aspect of the fingers, particularly within the joint creases), and mechanic hands (fissured, hyperkeratotic plaques along the thenar, radial, and ulnar aspects of the fingers, classically associated with the antisynthetase syndrome), among other more classic DM cutaneous findings.2 The unique clinical features of anti-MDA5-DM and its implications with regard to prognosis, given the association with highly morbid RP-ILD, further stresses the necessity for increased clinician awareness of this rare clinical syndrome so that earlier diagnosis and treatment can be initiated.

One such strategy to increase overall clinical awareness of rare disorders is through patient support groups and organizations. Myositis Support and Understanding (MSU) is a nonprofit, patient-led advocacy organization for IIM care teams. MSU identified a need to increase research defining the clinical characteristics of individual DM subtypes and created patient-led research teams to help spearhead this effort, hosting patient listening sessions and developing surveys to capture patient perceptions and experiences. Anti-MDA5-DM was felt to be one of the least characterized subtypes in their organization; therefore, a survey was created and distributed, with the goals to better understand the characteristics of anti-MDA5-DM, show capabilities to meaningfully collect data from a specific cohort, and create a profile of anti-MDA5-DM that could be useful in determining more successful management, treatment, and clinical trial design.

This study was reviewed by the Johns Hopkins Institutional Review Board (IRB00407349) and was deemed to be exempt. The survey design was adapted from a juvenile DM patient survey by McCann et al.3 The link was distributed throughout MSU’s multiple myositis groups, with an estimated reach of 5000 patients with IIM. A total of 46 participants responded using an anonymous Google form between December 8, 2022, and January 11, 2023; no personal information related to name or contact information was requested. Data collected included demographic information, additional positive autoantibody testing, presence of overlap autoimmune diseases, current pharmacotherapies, diagnostic tools used, symptoms over disease course, subjective muscle compromise, attitudes toward coronavirus disease 2019 (COVID-19) vaccination, and barriers to clinical trial participation.

Forty-three respondents were ultimately included in the analysis; 3 participants who reported negative anti-MDA5 autoantibody testing were excluded (see Table 1 for full demographic information). The majority of respondents were female (84%), identified as White (74%), and were from the United States (74%). More than half of respondents (58%) reported obtaining a diagnosis within < 6 months from symptom onset. There was high variability in the ages at diagnosis, as well as with reported current therapies (although a plurality did report active oral steroid use, 54%). Several respondents reported diagnoses of other autoimmune diseases or separate autoantibody positivity in addition to the anti-MDA5 autoantibody.

Demographic, autoantibody, and medications of anti-MDA5-DM survey participants (n = 43).

Table 2 shows the full results of this survey; responses regarding diagnostic testing and symptom profile with only 1 respondent were not included in this analysis. A wide range of diagnostic testing was reported, although over half of respondents reported the use of serum muscle enzymes and skin tissue sampling to aid in diagnosis (74% and 58%, respectively). Reported use of pulmonary function testing and imaging was also common, although interestingly, diagnostic imaging or procedural testing of the musculature was reported in less than a quarter of respondents. Whereas all respondents reported a positive anti-MDA5 autoantibody test, only 81% of patients specifically reported the use of a full myositis antibody laboratory panel at some point in their disease course.

Results of the patient survey with reported anti-MDA5 antibody-associated dermatomyositis (n = 43).

Regarding symptoms specifically present at the time of diagnosis, a vast majority (93%) reported active skin issues such as rashes or itching. Subjective muscle weakness (74%), pain (72%), cutaneous and oral ulcerations (58%), and arthritis (56%) were the next most common symptoms to be present. Lung involvement was less commonly reported, with only 16% reporting RP-ILD, and an additional 30% reporting the presence of ILD (though not specifically the rapidly progressive phenotype). Following diagnosis, dermatologic manifestations remained an active issue in most respondents, who reported nonspecific skin rashes (88%), heliotrope rash (77%), and/or mechanic hands (74%). Other common skin manifestations included Gottron papules/sign (67%), itching (63%), nailfold capillary changes (61%), and oral or cutaneous ulcerations (54%). A plurality of respondents (67%) reported the presence of pain as an extramuscular manifestation of their disease, followed by arthritis (56%) and non–RP-ILD (47%). Constitutional or nonspecific symptoms were highly prevalent throughout the cohort, with fatigue the most common (88%), followed by exercise intolerance (56%), and brain fog (56%). Respondents were asked to subjectively rate their overall muscle compromise from their disease on a scale of 0 to 10, with a score of 0 indicating no subjective compromise and a score of 10 indicating maximal muscle compromise. The mean score was 3.8, with a median of 4.

Less than half of respondents reported a history of prior SARS-CoV-2 infection (44%); a quarter of these patients tested positive for the anti-MDA5 autoantibody at some point after their infection. Twenty percent of these respondents also reported subsequent prolonged symptoms, which they associated with long-COVID. Vaccination rates overall were variable, with 14% stating that they were completely unvaccinated against SARS-CoV-2, and a plurality (35%) reporting having received ≥ 3 booster vaccines in addition to the original primary vaccine series.

Only 1 respondent reported having participated in a clinical trial for a myositis drug. When inquired about factors affecting participation in a clinical trial, more than half of respondents reported concerns about potentially receiving a placebo therapy (54%); other common concerns included health risks to potentially be unable to continue their currently prescribed therapies as well as inconvenience to travel to the study site (both reported by 44% of respondents). Only 1 respondent reported concern about the risk of the trialing drugs specifically.

To the best of our knowledge, this study is the first to gather patient insights regarding disease manifestations, clinical evaluations, and perspectives on clinical trial participation within a single MSA cohort. Published population and clinical data for anti-MDA5-DM is limited to relatively small cohorts of patients, given the estimated overall low incidence of nonspecific DM in the general population. This rarity is underlined by a recent cohort study4 that indicates an incidence of only 1.1 per 100,000 person-years, with anti-MDA5 antibody–positive patients comprising only a subset of these cases. Patient survey studies, such as this one with a 43-patient cohort, represent an underutilized opportunity to expand clinical knowledge of rare diseases. Surveying can offer critical clinical insights into disease phenotyping, variability of treatment strategies across healthcare providers, and patient attitudes. This specific antibody disease characterization is clinically valuable, facilitating heightened clinician awareness of this DM phenotype and potentially enabling earlier diagnoses and treatment initiation. It also provides beneficial prognostic information for clinicians and patients.

However, there are limitations to this dataset. As it is observational survey data, we are unable to verify patient responses with medical records. Also, myositis often suffers from high misdiagnosis rates, which may have led to respondents without true DM to take part in this survey. Yet, the specificity of MSA in a proper clinical context could lessen this overall effect, especially given that our data collection focused on patients reporting anti-MDA5 antibody positivity. The demographic trends in our dataset, featuring a higher proportion of female individuals and an increased diagnosis incidence within the 40- to 59-year age range (contrasting with most other non–anti-MDA5 MSA cohorts, where diagnosis incidence rises with age), suggest suitable population sampling. This is further strengthened by the high reported rates of specific skin manifestations typically associated with anti-MDA5-DM, such as mechanic hands and ulcerations.1,2,5

Importantly, the data on barriers to clinical trial participation for this rare disease are highly significant. The data from our study could help shape future trial designs by improving understanding of significant recruitment obstacles and encouraging increased participation, potentially leading to trials that can accurately assess the therapeutic efficacy of individual interventions. This would, in turn, inform clinical care.

We believe this study could be the foundation for additional projects for DM subtypes, incorporating the patient voice to help inform other stakeholders of unmet needs and underscoring crucial clinical awareness about disease phenotyping and the variability of treatment approaches, prompting future research agendas.

We thank the participants of the MSU’s anti-MDA5 DM survey, their caregivers, families, and the supporters of the myositis community.