Extracorporeal membrane oxygenation for idiopathic inflammatory myopathy-associated interstitial lung disease: a narrative review

Introduction

Idiopathic inflammatory myopathy (IIM), or myositis, represents a group of rare, heterogeneous, multi-system autoimmune diseases, encompassing subtypes such as dermatomyositis (DM), polymyositis (PM), and antisynthetase syndrome (ASS). While primarily characterized by skeletal muscle and skin involvement, IIM frequently affects other organs, with interstitial lung disease (ILD) standing as its most common and consequential extramuscular manifestation (1). The incidence of idiopathic inflammatory myopathy-associated interstitial lung disease (IIM-ILD) varies by ethnicity, geographic region, IIM subtype, and myositis-specific antibody profile (1,2). Globally, approximately 41% of DM/PM cases are complicated by ILD (2). The clinical course of IIM-ILD can be slowly or rapidly progressive. Notably, rapidly progressive ILD (RP-ILD) represents the most severe complication, bearing a grave prognosis with reported six-month mortality rates of 40–60% in Asian cohorts (3-5), establishing itself as a leading cause of death in IIM.

For patients with IIM-ILD who progress to refractory respiratory failure, treatment options are severely limited, prompting consideration of advanced life-support modalities such as extracorporeal membrane oxygenation (ECMO). ECMO use in this specific context presents distinct therapeutic challenges due to the high mortality rate (6) and the often irreversible nature of the underlying lung injury (7).

These profound clinical and ethical challenges have resulted in scarce and fragmented experience with ECMO in this specific context, leaving clinicians with limited evidence to guide their decision-making. Given the extreme scarcity of clinical experience and evidence, this review aims to synthesize the existing literature on ECMO in IIM-ILD, summarize the current state of knowledge, outline critical clinical challenges, and inform clinical decision-making and future investigative efforts. We present this article in accordance with the Narrative Review reporting checklist (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1-2490/rc).

Methods

A systematic search was performed on the MEDLINE database via the PubMed interface from its inception through August 31, 2025. Keywords included “myositis”, “idiopathic inflammatory myopathy”, “dermatomyositis”, “amyopathic dermatomyositis”, “polymyositis”, “antisynthetase syndrome”, “melanoma differentiation-associated protein 5”, “melanoma Differentiation-associated Gene 5”, “MDA-5”, “MDA5”, “interstitial lung disease*”, “Lung Diseases, Interstitial”, “rapidly progressive interstitial lung disease”, “rapid progressive interstitial lung disease”, “interstitial pneumonia”, “interstitial pneumonitis”, “pulmonary fibrosis”, “lung fibrosis”, “RP-ILD”, “RPILD”, “extracorporeal membrane oxygenation*”, “extracorporeal life support*”, “ECMO”, “ECLS”, “lung transplantation”, “pulmonary transplantation”, and “lung transplant”. Studies were eligible for inclusion if they were published in English in peer-reviewed journals and the full text was accessible. The exclusion criteria included studies involving patients under 18 years of age and those from which individual patient data could not be extracted. The search strategy is detailed in Table 1.

ECMO in IIM-ILD: rationale and potential benefits

Creating a therapeutic window

ECMO does not directly treat the underlying autoimmune process; rather, it “buys time” for other interventions to take effect. In patients with IIM-ILD and life-threatening respiratory failure, ECMO serves as a critical therapeutic window by providing temporary cardiopulmonary support. This therapeutic window serves one of two potential objectives: allowing time for aggressive immunosuppressive therapy to take effect or bridging the patient to lung transplantation (8). Notably, these divergent goals—recovery versus transplantation—are associated with markedly different survival outcomes, as detailed in the Clinical outcomes and patient selection section.

Protecting the lungs and circulation

Mechanical ventilation in severe IIM-ILD often necessitates high airway pressure and oxygen concentration, significantly increasing the risk of ventilator-induced lung injury (VILI) (9,10). VILI can, in turn, exacerbate the primary disease (11). ECMO maintains adequate gas exchange while facilitating an ultra-protective ventilatory strategy, minimizing the risk of aggravating the underlying chronic lung disease and helping prevent or alleviate mechanical ventilation-induced right heart dysfunction. A recent retrospective study reported a marked reduction in plateau pressures—from 18–26 to 10–18 cmH₂O—following the initiation of ECMO (12). Consequently, some researchers advocate for the early initiation of ECMO in patients with RP-ILD and severe respiratory failure to avoid complications associated with invasive mechanical ventilation, such as pneumothorax and mediastinal emphysema (13,14).

Awake ECMO strategy

For carefully selected patients—those with potentially reversible causes (e.g., acute infection superimposed on chronic ILD) or those who are potential lung transplantation candidates—an “awake ECMO” strategy can be employed to avoid intubation and its associated risks (7,15). This approach allows patients to remain conscious, engage in active rehabilitation, and preserve essential functions such as oral feeding and spontaneous coughing, which may improve post-transplant outcomes (16). Fuehner et al. (17) demonstrated a significantly higher 6-month post-transplant survival rate in the awake ECMO group compared to a historical cohort on mechanical ventilation (80% vs. 50%). Additional benefits include a reduced incidence of ventilator-associated pneumonia, maintained social interaction, decreased sedative use, and prevention of muscle atrophy through early mobilization. However, supporting evidence remains limited to a few studies, and this strategy is not without potential drawbacks, such as increased intrapulmonary shunt from atelectasis and the risk of patient self-inflicted lung injury (P-SILI) from vigorous spontaneous breathing (7). Therefore, rigorous patient selection is mandatory.

ECMO in IIM-ILD: clinical outcomes and patient selection

ECMO as a bridge: transplantation vs. recovery

A synthesis of the available case reports and series (Table 2) reveals a dramatic disparity in outcomes based on the treatment objectives. Among the 33 patients bridged to lung transplantation, 29 survived (88%). In contrast, of the 66 patients managed with ECMO as a bridge to recovery, only 14 survived (21%). This trend is corroborated by the largest study to date—a retrospective analysis of the Extracorporeal Life Support Organization (ELSO) registry by Quinn et al. (49)—which reported a survival to discharge of 80% in transplanted patients versus 28% in those who were not. Collectively, these data indicate that the survival benefit of ECMO in IIM-ILD is predominantly realized when it is used as a bridge to lung transplantation. ECMO alone does not reverse RP-ILD progression, and outcomes are uniformly poor when transplantation is not pursued (15,49).

Prognostic factors

The prognosis of patients with IIM-ILD on ECMO varies substantially based on underlying myositis-specific antibodies. Anti-melanoma differentiation-associated gene 5 antibody-positive (anti-MDA5 Ab+) DM carries an exceptionally grave prognosis. In a recent series, all seven anti-MDA5 Ab+ patients with ARF died despite VV ECMO and aggressive immunosuppression (12). Rubin et al. reported only 11% survival in a cohort where 67% of patients were anti-MDA5 Ab+ (6). Serial antibody titers may offer dynamic prognostic information; declining titers have been linked to survival, while persistently high titers predict poor outcomes and post-transplant recurrence (30,39,50-53).. In contrast, ASS is associated with significantly better outcomes. The reported ICU mortality for ASS-related RP-ILD is 18% versus 84% for anti-MDA5 Ab+ DM (24). In the cohort by Bay et al., all patients with ASS who received VV ECMO survived to discharge (54).

Virus-associated RP-ILD represents a distinct subgroup with favorable recovery potential. Among COVID-19 patients, anti-MDA5 antibodies were detected in 48.2% of cases and correlated with hyperinflammation and RP-ILD (55). All three patients with virus-associated RP-ILD in a separate cohort were successfully weaned from ECMO (56), suggesting that ECMO can effectively bridge selected patients to recovery when a reversible trigger is identified.

Implications for patient selection

For most patients with IIM-ILD and severe respiratory failure, aggressive immunosuppressive therapy alone is insufficient to reverse lung damage, making lung transplantation the only definitive, life-saving intervention (25). In this context, ECMO’s primary value appears to be as a bridge to transplantation; it can facilitate salvage transplantation for patients not initially on the waiting list and enable inter-hospital transfer to specialized centers (57).

However, for patients ineligible for lung transplantation, the use of ECMO to prolong life is of questionable benefit and may increase patient and family burden. Therefore, a comprehensive pre-ECMO assessment that incorporates antibody status, serial titer trends, transplant candidacy, and potential reversibility is paramount. Treatment goals should be explicitly defined at initiation and reassessed daily. If these goals become unattainable, ECMO withdrawal should be considered, ideally with palliative care involvement.

Importantly, the poor average outcomes for IIM-ILD disease should not automatically exclude individual patients from a trial of immunosuppression. Early, intensive multidrug regimens may still induce remission for a subset of patients (12,58).

ECMO in IIM-ILD: practical challenges

Diagnostic delay and missed recognition

The early diagnosis of IIM-ILD continues to pose a persistent challenge in clinical practice. Delayed recognition, sometimes until after transplantation (19,27) or postmortem (29), or misdiagnosis (as allergic or infectious diseases) directly results in missed opportunities for timely immunosuppressive therapy and transplant referral.

The primary cause of this delay is the absence of classic extrapulmonary manifestations in certain subtypes. Although most patients with clinically amyopathic dermatomyositis (CADM) eventually develop characteristic skin lesions (59), ILD may precede cutaneous symptoms or occur in their absence (26,29,60-62). A French ICU-based retrospective study highlighted that over one-third of patients with ASS or anti-MDA5 Ab+ IIM lacked extrapulmonary manifestations at presentation (24). Therefore, a high index of suspicion is required, even in the absence of muscle or skin involvement.

Distinguishing IIM-ILD from ARDS and infection

In the absence of systemic clues, IIM-ILD, especially when manifesting as acute respiratory failure (ARF), is frequently misdiagnosed as acute respiratory distress syndrome (ARDS). A key distinguishing feature is the lack of a recognizable clinical trigger (e.g., pneumonia or sepsis) as required by the Berlin criteria for ARDS. Studies indicate that among patients meeting the Berlin criteria, 8% lack common risk factors, and within this subgroup, 80% remain without a definitive etiology; however, only 5% undergo immunological evaluation (63,64). For atypical ARDS cases without identifiable triggers, comprehensive diagnostic testing, including autoimmune serology, is strongly recommended to identify immune-mediated causes and guide targeted therapy (e.g., corticosteroids) (65).

Certain clinical, laboratory, and imaging patterns should raise suspicion of IIM-ILD. Intensivists managing patients with bilateral pulmonary infiltrates and rapidly progressive respiratory failure should maintain a high index of suspicion for autoimmune etiologies. Clinically, the scenario of “bilateral pneumonia without microbiological confirmation” coupled with a dissociation in inflammatory markers—elevated C-reactive protein but normal procalcitonin—strongly suggests a non-infectious inflammatory process and warrants an evaluation for autoimmune lung disease.

Imaging patterns provide valuable diagnostic clues. According to the American Thoracic Society guidelines, the presence of overlapping nonspecific interstitial pneumonia and organizing pneumonia patterns on high-resolution CT is highly suggestive of IIM. Furthermore, spontaneous pneumomediastinum in the context of acute hypoxemic respiratory failure is a recognized indicator of IIM-related RP-ILD (66). One retrospective study reported that all seven patients with anti-MDA5 Ab+ DM and RP-ILD developed pneumothorax or pneumomediastinum, most before ECMO initiation (12). Additionally, unexplained bilateral, patchy, asymmetric peribronchial consolidations on CT should prompt consideration of anti-MDA5-associated RP-ILD (61). Given the severity, some experts recommend that any RP-ILD of unknown origin be regarded as potentially anti-MDA5-related, with corresponding antibody screening performed (28,60).

Serological testing plays a pivotal role. The presence of specific autoantibodies is closely associated with ILD in IIM. Patients with antisynthetase antibodies frequently develop ILD (67), and anti-MDA5 Ab+ is a major risk factor for RP-ILD (68,69), with approximately 90% of anti-MDA5 Ab+ DM patients developing ILD, often in the form of CADM (70).

The diagnostic distinction between IIM-ILD and ARDS carries therapeutic and prognostic implications that extend beyond immunosuppression. For patients progressing to refractory respiratory failure, an accurate diagnosis is essential for appropriate ECMO candidacy and timely lung transplant referral. An unrecognized IIM-ILD that is labelled as “severe ARDS” may miss the narrow window for salvage therapy.

Optimizing immunosuppression during ECMO

The dilemma of immunosuppressive therapy

In patients with IIM-ILD who progress to ECMO, the response to pharmacological therapy distinguishes between eventual recovery, transplantation, or death. However, the window for disease control is narrow; by the time ECMO is required, irreversible lung injury may have already been established. Furthermore, intensive immunosuppression increases susceptibility to life-threatening infections, which may preclude further treatment escalation and worsen the outcomes (12). This reality has prompted a critical shift in clinical practice: the threshold for initiating multidrug immunosuppression should be substantially lowered in anti-MDA5 Ab+ patients, even in those with mild ILD, rather than reserved as a salvage strategy once ECMO is underway (12).

Combination strategies and drug selection

The standard first-line therapy for IIM-ILD consists of high-dose glucocorticoids (e.g., prednisone >1.0 mg·kg⁻¹·d⁻¹ or equivalent methylprednisolone) combined with one or more additional immunosuppressants. In refractory cases, particularly those who are positive for anti-Jo-1 or anti-MDA5 Ab+, biologic agents such as rituximab are often added upfront (1). Janus kinase (JAK) inhibitors have shown promise in small series. For example, three of five refractory anti-MDA5 Ab patients who failed glucocorticoids, cyclosporine, and cyclophosphamide survived after the addition of tofacitinib (10 mg/day), whereas all six controls who did not receive the drug died (71). A triple regimen including glucocorticoids, tacrolimus, and tofacitinib was also successfully used in a patient with ASS and RP-ILD requiring VV ECMO (23).

Although no universal consensus exists on the optimal combination, many experts advocate initiating multi-drug therapy at diagnosis. One proposed regimen includes high-dose glucocorticoids, an antimetabolite (mycophenolate mofetil or azathioprine), and a third agent, such as tacrolimus or rituximab, to rapidly induce remission (66). For anti-MDA5 Ab+ RP-ILD, alternatives include glucocorticoids combined with a calcineurin inhibitor (tacrolimus or cyclosporine), or a three-drug regimen consisting of glucocorticoids, a calcineurin inhibitor, and intravenous cyclophosphamide (72). A Japanese multicenter prospective study reported a 6-month survival rate of 89% with early initiation of this triple regimen compared with 33% under conventional step-up therapy (58). Accumulating evidence suggests that such intensive immunosuppression may improve outcomes in anti-MDA5 Ab+ DM with RP-ILD (73).

Despite these encouraging results in non-ECMO populations, the efficacy of intensive immunosuppression in patients who have already progressed to ECMO remains unproven. A recent study found no survival benefit among anti-MDA5 Ab+ RP-ILD patients who received aggressive combination therapy while on ECMO, likely reflecting their more critical baseline status and longer disease duration prior to treatment initiation (12).

Adjunctive therapies: plasma exchange (PE) and intravenous immunoglobulin (IVIG)

PE offers a theoretical advantage in anti-MDA5 Ab+ RP-ILD by directly removing pathogenic autoantibodies and inflammatory cytokines (74). Among 14 refractory patients treated with salvage PE, nine survived (75,76). Early PE (within two weeks) combined with intensive immunosuppression was associated with higher survival than immunosuppression alone (100% vs. 61%) (77), and PE improved 1-year survival in patients with early deterioration despite intensive therapy (100% vs. 25%) (78). An additional advantage is its feasibility in patients with active infection. However, procedural complications, including acute lung injury, must be weighed (79).

IVIG modulates Fc receptors, neutralizes autoantibodies, and inhibits complement activation (80). In a retrospective analysis of 48 anti-MDA5 Ab+ RP-ILD patients, the addition of IVIG to immunosuppressants was associated with higher 3-month remission and 6-month survival rates (81).

Whether these adjunctive therapies confer additional benefits specifically in ECMO-supported patients remains unknown and warrants dedicated investigation.

Pharmacokinetic considerations during ECMO

The optimization of immunosuppression during ECMO is further complicated by drug sequestration within the circuit. Lipophilic agents (high logP) and those with high plasma protein binding are particularly prone to reduced systemic availability (82,83). In the absence of robust evidence, dosing should be guided by physicochemical properties and, where available, therapeutic drug monitoring (84).

Potential risks of ECMO

ECMO support is not without significant risk. Common complications include bleeding (due to anticoagulation and coagulopathy), thromboembolic events such as stroke, and nosocomial infections, particularly ventilator-associated pneumonia and bloodstream infections. These complications can substantially affect patient outcomes and must be carefully weighed against the potential benefits. Furthermore, the prolonged duration of ECMO support may increase the risk of these adverse events, necessitating vigilant monitoring and multidisciplinary management. Furthermore, although ECMO effectively bridges patients to transplantation, it is not without long-term consequences. Studies have identified the use of ECMO prior to lung transplantation as a significant risk factor for postoperative mortality (85).

Future outlook

Looking ahead, numerous questions remain unresolved regarding the use of ECMO in IIM-ILD. Although selected patients have been successfully bridged to recovery or transplantation, the overall outcomes, particularly for those who do not receive a transplant, are sobering. We believe that progress will depend less on ECMO technology itself and more on how we integrate it into a broader, evidence-based, and ethically sound clinical framework. In our view, the following directions merit priority.

First, patient selection should move beyond crude measures of disease severity. Currently, we lack reliable markers to determine whether lung injury is potentially reversible. Therefore, we suggest that future investigations concentrate on integrating autoantibody profiles (especially anti-MDA5 Ab dynamics), serum biomarkers, serial HRCT patterns, and, where available, histopathology. The goal would be to build and validate predictive models that can, with reasonable accuracy, distinguish patients who might recover from those for whom ECMO would only delay an inevitable outcome. Registry-based machine learning approaches could be particularly valuable in this area.

Second, the optimal protocol of administering immunosuppression during ECMO is still largely guesswork. Controlled data are absent; most regimens are extrapolated from non-ECMO populations or borrowed from other autoimmune diseases. We see an urgent need for multicenter observational studies and eventually pragmatic trials that compare different combination strategies (e.g., calcineurin inhibitors versus rituximab, the addition of JAK inhibitors) specifically in the ECMO setting. Equally important is the systematic evaluation of adjunctive therapies such as PE and IVIG; current evidence is tantalizing but too fragmented to guide routine practice. In parallel, research into agents that actively promote lung repair, rather than merely suppress inflammation, could shift the paradigm, if successful, from transplantation to recovery.

Third, if transplantation is the destination, the journey is important. We advocate viewing ECMO not as a rescue of last resort but as a proactive, protocolized bridge that begins the moment a patient with progressive IIM-ILD is identified as a potential transplant candidate. This requires seamless multidisciplinary collaboration between intensivists, rheumatologists, pulmonologists, and transplant surgeons, a lesson repeatedly emphasized in successful center reports. Future research should also track long-term outcomes after transplantation, including graft survival, disease recurrence (particularly in anti-MDA5 Ab+ patients), and optimal post-transplant immunosuppression therapy. Without such data, we cannot determine whether a successful bridge truly translates into a meaningful life.

Finally, decisions regarding ECMO initiation and withdrawal remain profoundly difficult. We propose the development of dynamic prognostic tools that incorporate real-time clinical and biomarker data to support, not replace, shared decision-making with patients and families. Early integration of palliative care principles should become standard practice, not as a surrender but as a way to ensure that goals are continually re-evaluated. Clear, institution-endorsed ethical frameworks for ECMO withdrawal are urgently needed when treatment goals become unattainable; leaving these decisions to ad hoc bedside judgment risks both inconsistency and moral distress.

Limitations

We acknowledge that this review is subject to several important limitations, many of which stem from the nature of the available evidence itself.

First, publication bias is a prominent issue in the existing literature in this field. The evidence base consists almost entirely of case reports and small case series, formats that disproportionately favour positive outcomes. Clinicians are far more likely to report a successful ECMO run that led to recovery or transplantation than a case in which the patient died or ECMO was withdrawn. This bias is not hypothetical; in our own synthesis, we noted that among 33 patients bridged to transplantation, 29 survived (88%). It is plausible that an unknown number of unsuccessful bridging attempts, where patients deteriorated on ECMO and were removed from the transplant list or died before a donor became available, simply never appeared in the literature. Consequently, the true survival rate for bridge-to-transplant may be substantially lower than the published figures suggest.

Second, aside from potential biological differences (such as the poor prognosis inherently associated with anti-MDA5 Ab+), survivor bias has profoundly influenced the findings of this review at multiple levels: patients receiving ECMO as a bridge to transplantation underwent multiple rounds of “survivor selection”, whereas those receiving ECMO as a bridge to recovery bore the full burden of all unsuccessful outcomes that could not be concealed by any subsequent intervention. Consequently, the prognostic disparity between the two groups has been systematically magnified in the existing literature. Future studies should employ intention-to-treat analysis and mandate the reporting of all initiated ECMO cases (regardless of whether transplantation ultimately occurred) to more accurately assess the true value of ECMO under different therapeutic strategies.

Third, center-level practice variations profoundly limit generalizability. ECMO for IIM-ILD is performed only in highly specialised centres, and what is reported from a high-volume centre with a dedicated multidisciplinary team, rapid access to transplantation, and aggressive immunosuppressive protocols may not be achievable in a centre with fewer resources or different practice patterns. For example, the excellent outcomes reported by Bay et al. (54) for patients with ASS may reflect not only the underlying disease but also centre-specific expertise in patient selection, ventilator management, and post-ECMO care. Conversely, the dismal outcomes in some anti-MDA5 Ab+ series (12) could be influenced by delays in diagnosis, differences in ECMO initiation, or varying thresholds for continuing support. We cannot disentangle disease biology from centre effects with the available data.

Fourth, when interpreting the markedly lower survival rate observed in patients receiving ECMO as a bridge to recovery compared to those bridged to transplantation, significant confounding by indication must be acknowledged. Patients in the bridge-to-recovery cohort are frequently those deemed ineligible for lung transplantation due to factors such as advanced age, significant comorbidities, or an overwhelmingly severe physiological state at presentation. These very factors are independently associated with poor prognosis and may have contributed substantially to the dismal outcomes in this group, rather than the failure of ECMO as a supportive modality per se. This review cannot disentangle the effect of ECMO from the impact of these underlying patient characteristics, underscoring the need for future studies with better-matched control groups.

Fifth, the reported survival outcomes were primarily limited to survival to hospital discharge or the end of the follow-up, rather than uniform long-term post-transplant survival at fixed time points such as 1- or 3-year survival. Furthermore, the duration of post-transplant follow-up varied considerably across the included studies, which prevented a reliable comparison of long-term survival duration. These limitations highlight the need for future investigations with standardized follow-up protocols and consistent survival endpoints.

Beyond these biases, the heterogeneity of the primary studies precludes any meaningful meta-analysis or comparative effectiveness assessment. Definitions of RP-ILD, criteria for ECMO initiation, immunosuppressive regimens, and transplantation policies all vary widely. Therefore, what we have presented is a narrative synthesis-a summary of what has been reported-not a quantitative estimate of what should be expected.

Conclusions

This review synthesizes the current evidence on the use of ECMO in patients with IIM-ILD and refractory respiratory failure. The available data, derived predominantly from case reports and small series, indicate that ECMO serves primarily as a viable bridge to lung transplantation rather than to recovery. Among reported cases, survival to discharge is substantially higher in patients who undergo transplantation while on ECMO compared to those managed with a bridge-to-recovery strategy. However, this observation must be interpreted with caution, as the existing literature is subject to significant publication bias, survivor bias, and center-level practice variation.

The extreme heterogeneity of IIM-ILD—driven by myositis-specific antibody profiles, clinical phenotypes, and the presence of reversible triggers—underscores that patient selection is paramount. Anti-MDA5 Ab+ DM carries an exceptionally grave prognosis even with ECMO support, whereas patients with ASS or virus-associated RP-ILD may achieve favorable outcomes. These distinctions should inform both the decision to initiate ECMO and the ongoing assessment of treatment goals.

Several critical challenges persist. Diagnostic delay remains common, particularly in patients without classic extrapulmonary manifestations, and may result in missed opportunities for timely immunosuppression or transplant referral. Optimal immunosuppressive regimens during ECMO support are undefined, and pharmacokinetic alterations induced by the extracorporeal circuit further complicate management. Adjunctive therapies such as PE and IVIG show promise but lack systematic evaluation in this specific population.

Looking forward, progress will depend less on technological refinement and more on integrating ECMO into proactive, multidisciplinary treatment pathways. Future research priorities include developing validated predictive models to distinguish reversible from irreversible lung injury, standardizing immunosuppressive protocols through multicenter collaboration, and establishing ethical frameworks to guide ECMO initiation and withdrawal. Without such efforts, ECMO risks remaining a costly and ethically challenging intervention of last resort rather than a meaningful strategy that improves long-term outcomes for this complex patient population.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the Narrative Review reporting checklist. Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1-2490/rc

Peer Review File: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1-2490/prf

Funding: This study was supported by the Tianjin Science and Technology Project (No. 21YCFBJC01200), the Tianjin Health Research Project (No. TJWJ2025XK006), the Research Project on the Integration of Traditional Chinese Medicine and Western Medicine by Tianjin Health Commission (No. 2023221), and the Tianjin Key Research Projects in the Field of Traditional Chinese Medicine (No. 2025019).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1-2490/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Respiratory Council of Chinese Research Hospital Association. Chinese expert-based consensus statement on diagnosis and treatment of idiopathic inflammatory myopathy associated interstitial lung disease. Chin J Tuberc Respir Dis 2022;45:635-50. [PubMed]
2. Sun KY, Fan Y, Wang YX, et al. Prevalence of interstitial lung disease in polymyositis and dermatomyositis: A meta-analysis from 2000 to 2020. Semin Arthritis Rheum 2021;51:175-91. [Crossref] [PubMed]
3. Hamaguchi Y, Kuwana M, Hoshino K, et al. Clinical correlations with dermatomyositis-specific autoantibodies in adult Japanese patients with dermatomyositis: a multicenter cross-sectional study. Arch Dermatol 2011;147:391-8. [Crossref] [PubMed]
4. Koga T, Fujikawa K, Horai Y, et al. The diagnostic utility of anti-melanoma differentiation-associated gene 5 antibody testing for predicting the prognosis of Japanese patients with DM. Rheumatology (Oxford) 2012;51:1278-84. [Crossref] [PubMed]
5. Ye S, Chen XX, Lu XY, et al. Adult clinically amyopathic dermatomyositis with rapid progressive interstitial lung disease: a retrospective cohort study. Clin Rheumatol 2007;26:1647-54. [Crossref] [PubMed]
6. Rubin J, Black KE, Hallowell RW, et al. Veno-Venous Extracorporeal Membrane Oxygenation for Myositis-Associated Rapidly Progressive Interstitial Lung Disease. Chest 2021;160:2163-7. [Crossref] [PubMed]
7. Rozencwajg S, Schmidt M. Extracorporeal membrane oxygenation for interstitial lung disease: what is on the other side of the bridge? J Thorac Dis 2016;8:1918-20. [Crossref] [PubMed]
8. Romero-Bueno F, Diaz Del Campo P, Trallero-Araguás E, et al. Recommendations for the treatment of anti-melanoma differentiation-associated gene 5-positive dermatomyositis-associated rapidly progressive interstitial lung disease. Semin Arthritis Rheum 2020;50:776-90. [Crossref] [PubMed]
9. Anzueto A, Frutos-Vivar F, Esteban A, et al. Incidence, risk factors and outcome of barotrauma in mechanically ventilated patients. Intensive Care Med 2004;30:612-9. [Crossref] [PubMed]
10. Rachmale S, Li G, Wilson G, et al. Practice of excessive F(IO(2)) and effect on pulmonary outcomes in mechanically ventilated patients with acute lung injury. Respir Care 2012;57:1887-93. [Crossref] [PubMed]
11. Martin TR, Nakamura M, Matute-Bello G. The role of apoptosis in acute lung injury. Crit Care Med 2003;31:S184-8. [Crossref] [PubMed]
12. Wang L, Wu X, He S, et al. Comparison of the use of venovenous extracorporeal membrane oxygenation in anti-melanoma differentiation-associated protein 5 positive dermatomyositis and other systemic rheumatic diseases associated with acute respiratory failure based on a single-center retrospective study. J Thorac Dis 2024;16:6516-24. [Crossref] [PubMed]
13. Alqatari S, Riddell P, Harney S, et al. MDA-5 associated rapidly progressive interstitial lung disease with recurrent Pneumothoraces: a case report. BMC Pulm Med 2018;18:59. [Crossref] [PubMed]
14. Zhou M, Ye Y, Yan N, et al. Noninvasive positive pressure ventilator deteriorates the outcome of pneumomediastinum in anti-MDA5 antibody-positive clinically amyopathic dermatomyositis. Clin Rheumatol 2020;39:1919-27. [Crossref] [PubMed]
15. Trudzinski FC, Kaestner F, Schäfers HJ, et al. Outcome of Patients with Interstitial Lung Disease Treated with Extracorporeal Membrane Oxygenation for Acute Respiratory Failure. Am J Respir Crit Care Med 2016;193:527-33. [Crossref] [PubMed]
16. Keshavamurthy S, Bazan V, Tribble TA, et al. Ambulatory extracorporeal membrane oxygenation (ECMO) as a bridge to lung transplantation. Indian J Thorac Cardiovasc Surg 2021;37:366-79. [Crossref] [PubMed]
17. Fuehner T, Kuehn C, Hadem J, et al. Extracorporeal membrane oxygenation in awake patients as bridge to lung transplantation. Am J Respir Crit Care Med 2012;185:763-8. [Crossref] [PubMed]
18. Leclair V, Labirua-Iturburu A, Lundberg IE. Successful Lung Transplantation in a Case of Rapidly Progressive Interstitial Lung Disease Associated with Antimelanoma Differentiation-associated Gene 5 Antibodies. J Rheumatol 2018;45:581-3. [Crossref] [PubMed]
19. Deitchman AR, Kalchiem-Dekel O, Todd N, et al. Rapidly progressive interstitial lung disease due to anti-melanoma differentiation associated protein-5 requiring a bilateral lung transplant, and complicated by kennel cough. Respir Med Case Rep 2019;28:100886. [Crossref] [PubMed]
20. Górka J, Szczeklik W, Włudarczyk A, et al. Rapidly progressive interstitial lung fibrosis in a patient with amyopathic dermatomyositis and anti MDA5 antibodies. Pol Arch Med Wewn 2015;125:685-6. [Crossref] [PubMed]
21. Broomé M, Palmér K, Scherstén H, et al. Prolonged extracorporeal membrane oxygenation and circulatory support as bridge to lung transplant. Ann Thorac Surg 2008;86:1357-60. [Crossref] [PubMed]
22. Huang J, Liu C, Zhu R, et al. Combined usage of extracorporeal membrane oxygenation and double filtration plasmapheresis in amyopathic dermatomyositis patient with severe interstitial lung disease: A case report. Medicine (Baltimore) 2018;97:e10946. [Crossref] [PubMed]
23. Pineton de Chambrun M, Hervier B, Chauveau S, et al. Tofacitinib in antisynthetase syndrome-related rapidly progressive interstitial lung disease. Rheumatology (Oxford) 2020;59:e142-3. [Crossref] [PubMed]
24. Vuillard C, Pineton de Chambrun M, de Prost N, et al. Clinical features and outcome of patients with acute respiratory failure revealing anti-synthetase or anti-MDA-5 dermato-pulmonary syndrome: a French multicenter retrospective study. Ann Intensive Care 2018;8:87. [Crossref] [PubMed]
25. Huang K, Vinik O, Shojania K, et al. Clinical spectrum and therapeutics in Canadian patients with anti-melanoma differentiation-associated gene 5 (MDA5)-positive dermatomyositis: a case-based review. Rheumatol Int 2019;39:1971-81. [Crossref] [PubMed]
26. Gu Q, Diao M, Hu W, et al. Case Report: Extracorporeal Membrane Oxgenation for Rapidly Progressive Interstitial Lung Disease Associated With Clinically Amyopathic Dermatomyositis in a Post-partum Woman. Front Med (Lausanne) 2021;8:742823. [Crossref] [PubMed]
27. Marchiset A, Neuville M, Voiriot G, et al. High-Emergency Lung Transplantation for Interstitial Lung Disease Associated With Anti-MDA5 Dermatomyositis: A Case Report. Transplant Proc 2021;53:2613-5. [Crossref] [PubMed]
28. Ismail D, Ezzy F, Ayesha B. Two fatal cases of anti-melanoma differentiation-associated gene 5 antibody (anti-MDA5) rapidly progressive interstitial lung disease (RP-ILD): Exploring pitfalls and differences. Respir Med Case Rep 2025;55:102224. [Crossref] [PubMed]
29. Aoyama J, Hayashi H, Yajima C, et al. Anti-MDA5 antibody-positive rapidly progressive interstitial pneumonia without cutaneous manifestations. Respir Med Case Rep 2019;26:193-6. [Crossref] [PubMed]
30. Lian QY, Chen A, Zhang JH, et al. Lung transplantation for anti-MDA5-positive dermatomyositis-associated rapid progressive interstitial lung disease: report of two cases and review of the literature. Clin Rheumatol 2023;42:941-7. [Crossref] [PubMed]
31. Huang K, Levy RD, Avina-Zubieta JA. Successful lung transplant in rapid progressive interstitial lung disease associated with anti-melanoma differentiation associated gene 5. Rheumatology (Oxford) 2020;59:2161-3. [Crossref] [PubMed]
32. Jhajj AS, Shun Yeung JH, To F. Spontaneous Pneumomediastinum due to Anti-Melanoma Differentiation-Associated Protein 5 Requiring a Bilateral Lung Transplant. Case Rep Rheumatol 2021;2021:6097183. [Crossref] [PubMed]
33. Pacot L, Pouchot J, De Prost N, et al. Interstitial Lung Disease-Complicated Anti-MDA5 Antibody in Clinically Amyopathic Dermatomyositis Patients: Report of Two Cases With Distinct Clinical Features. Front Med (Lausanne) 2020;7:77. [Crossref] [PubMed]
34. Kim J, Kim YW, Lee SM, et al. Successful lung transplantation in a patient with dermatomyositis and acute form of interstitial pneumonitis. Clin Exp Rheumatol 2009;27:168-9. [PubMed]
35. Li ZY, Gill E, Mo F, et al. Double anti-PL-7 and anti-MDA-5 positive Amyopathic Dermatomyositis with rapidly progressive interstitial lung disease in a Hispanic patient. BMC Pulm Med 2020;20:220. [Crossref] [PubMed]
36. Zhang C, Guo J, Ye G, et al. Successful lung transplantation in RPILD associated with anti-MDA5ab+: A case report. Medicine (Baltimore) 2025;104:e41408. [Crossref] [PubMed]
37. Al-Husayni F, Munshi A, Qanash S, et al. Clinically Amyopathic Dermatomyositis With Rapid Progressive Interstitial Lung Disease Diagnosed in a Patient on Extracorporeal Membrane Oxygenation. Cureus 2022;14:e27839. [Crossref] [PubMed]
38. Leveque T, Pavlidi A, Lacoste-Palasset T, et al. A 24-Year-Old Woman With Cough, Arthralgia, and Skin Ulcerations. Chest 2023;163:e223-9. [Crossref] [PubMed]
39. Hage R, Chatzidaki E, Clarenbach CF, et al. Clinical characteristics and outcomes in patients with Anti-MDA5 positive interstitial lung disease: A case series from a lung transplant center. Respir Med Case Rep 2025;57:102265. [Crossref] [PubMed]
40. Zheng B, Eline E, Xu L, et al. Extracorporeal membrane oxygenation for acute lung injury in idiopathic inflammatory myopathies-a potential lifesaving intervention. Rheumatology (Oxford) 2025;64:2204-8. [Crossref] [PubMed]
41. Borio G, Terracciano C, Buttafava F, et al. Skin Rash and Interstitial Pneumonia Can Be a Fatal Combination: A Rare Case of Anti-Melanoma Differentiation-Associated Gene 5 (MDA5)-Associated Interstitial Lung Disease. Eur J Case Rep Intern Med 2021;8:002860. [Crossref] [PubMed]
42. Shah A, Patel SR. Acute Onset Anti-Synthetase Syndrome With Pericardial Effusion and Non-Specific Interstitial Pneumonia. J Clin Med Res 2016;8:683-7. [Crossref] [PubMed]
43. Onose T, Kido T, Okada I, et al. An autopsy case of anti-MDA5 antibody-positive amyopathic dermatomyositis with an initial manifestation of panniculitis on the left upper arm. Mod Rheumatol Case Rep 2023;8:86-90. [Crossref] [PubMed]
44. Truong L, Youssef FA, Ajaz U, et al. Extracorporeal Membrane Oxygenation Used in the Treatment of Rapidly Progressive Interstitial Pneumonia in a Patient With Amyopathic Dermatomyositis and Positive Melanoma Differentiation-Associated Gene 5. J Clin Rheumatol 2021;27:e215-7. [Crossref] [PubMed]
45. Oda N, Taniguchi A, Aokage T, et al. Fulminant Respiratory Failure Caused by Anti-asparaginyl tRNA Synthetase (Anti-KS) Antibody Syndrome-related Interstitial Lung Disease. Intern Med 2022;61:3409-14. [Crossref] [PubMed]
46. Sampson C, Taylor J, Dyson L, et al. Life-threatening respiratory failure requiring extra-corporeal membrane oxygenation secondary to the anti-synthetase syndrome. J Intensive Care Soc 2021;22:83-7. [Crossref] [PubMed]
47. Zhang H, Yue J, Hou X, et al. Rapidly progressive interstitial lung disease combined with pneumocystis jiroveci pneumonia in a patient with single anti-TIF-1γ antibody positive dermatomyositis in the context of an underlying tumor. BMC Pulm Med 2023;23:248. [Crossref] [PubMed]
48. Bay P, Pineton de Chambrun M, Roux A, et al. Extracorporeal life support allows lung transplant in anti-MDA5+ rapidly progressive interstitial lung disease. Eur Respir J 2022;59:2102968. [Crossref] [PubMed]
49. Quinn RE, Riedl R, Rycus PT, et al. Extracorporeal Membrane Oxygenation Support for Interstitial Lung Disease in Idiopathic Inflammatory Myopathies: An ELSO Registry Analysis. ASAIO J 2023;69:e96-9. [Crossref] [PubMed]
50. Gangadharan H, Seetha AP, Musthafa S, et al. Clinical Characteristics and Outcomes of Patients with Anti-MDA5 Antibody Associated Rapidly Progressive Interstitial Lung Disease (RP-ILD): A Case Series. Mediterr J Rheumatol 2024;35:668-79. [Crossref] [PubMed]
51. Xu YT, Zhang YM, Yang HX, et al. Evaluation and validation of the prognostic value of anti-MDA5 IgG subclasses in dermatomyositis-associated interstitial lung disease. Rheumatology (Oxford) 2022;62:397-406. [Crossref] [PubMed]
52. Matsushita T, Mizumaki K, Kano M, et al. Antimelanoma differentiation-associated protein 5 antibody level is a novel tool for monitoring disease activity in rapidly progressive interstitial lung disease with dermatomyositis. Br J Dermatol 2017;176:395-402. [Crossref] [PubMed]
53. Endo Y, Koga T, Ishida M, et al. Recurrence of anti-MDA5 antibody-positive clinically amyopathic dermatomyositis after long-term remission: A case report. Medicine (Baltimore) 2018;97:e11024. [Crossref] [PubMed]
54. Bay P, Lebreton G, Mathian A, et al. Outcomes of severe systemic rheumatic disease patients requiring extracorporeal membrane oxygenation. Ann Intensive Care 2021;11:29. [Crossref] [PubMed]
55. Wang G, Wang Q, Wang Y, et al. Presence of Anti-MDA5 Antibody and Its Value for the Clinical Assessment in Patients With COVID-19: A Retrospective Cohort Study. Front Immunol 2021;12:791348. [Crossref] [PubMed]
56. Bay P, Mathian A, Uzunhan Y, et al. Extracorporeal Membrane Oxygenation for Myositis-Associated Rapidly Progressive-Interstitial Lung Disease: Not All Who Wander Are Lost. Chest 2021;160:e680-1. [Crossref] [PubMed]
57. Hoopes CW, Kukreja J, Golden J, et al. Extracorporeal membrane oxygenation as a bridge to pulmonary transplantation. J Thorac Cardiovasc Surg 2013;145:862-7; discussion 867-8. [Crossref] [PubMed]
58. Tsuji H, Nakashima R, Hosono Y, et al. Multicenter Prospective Study of the Efficacy and Safety of Combined Immunosuppressive Therapy With High-Dose Glucocorticoid, Tacrolimus, and Cyclophosphamide in Interstitial Lung Diseases Accompanied by Anti-Melanoma Differentiation-Associated Gene 5-Positive Dermatomyositis. Arthritis Rheumatol 2020;72:488-98. [Crossref] [PubMed]
59. Concha JSS, Tarazi M, Kushner CJ, et al. The diagnosis and classification of amyopathic dermatomyositis: a historical review and assessment of existing criteria. Br J Dermatol 2019;180:1001-8. [Crossref] [PubMed]
60. González-Moreno J, Raya-Cruz M, Losada-Lopez I, et al. Rapidly progressive interstitial lung disease due to anti-MDA5 antibodies without skin involvement: a case report and literature review. Rheumatol Int 2018;38:1293-6. [Crossref] [PubMed]
61. Tamai K, Tachikawa R, Otsuka K, et al. Early pulmonary involvement of anti-CADM-140 autoantibody-positive rapidly progressive interstitial lung disease preceding typical cutaneous symptoms. Intern Med 2014;53:2515-9. [Crossref] [PubMed]
62. Ortiz-Santamaria V, Babot A, Ferrer C. Anti-MDA5-positive dermatomyositis: an emerging entity with a variable clinical presentation. Scand J Rheumatol 2017;46:509-11. [Crossref] [PubMed]
63. Gibelin A, Parrot A, Maitre B, et al. Acute respiratory distress syndrome mimickers lacking common risk factors of the Berlin definition. Intensive Care Med 2016;42:164-72. [Crossref] [PubMed]
64. de Prost N, Pham T, Carteaux G, et al. Etiologies, diagnostic work-up and outcomes of acute respiratory distress syndrome with no common risk factor: a prospective multicenter study. Ann Intensive Care 2017;7:69. [Crossref] [PubMed]
65. Papazian L, Calfee CS, Chiumello D, et al. Diagnostic workup for ARDS patients. Intensive Care Med 2016;42:674-85. [Crossref] [PubMed]
66. Jablonski R, Bhorade S, Strek ME, et al. Recognition and Management of Myositis-Associated Rapidly Progressive Interstitial Lung Disease. Chest 2020;158:252-63. [Crossref] [PubMed]
67. Betteridge Z, McHugh N. Myositis-specific autoantibodies: an important tool to support diagnosis of myositis. J Intern Med 2016;280:8-23. [Crossref] [PubMed]
68. Zhang L, Wu G, Gao D, et al. Factors Associated with Interstitial Lung Disease in Patients with Polymyositis and Dermatomyositis: A Systematic Review and Meta-Analysis. PLoS One 2016;11:e0155381. [Crossref] [PubMed]
69. Moghadam-Kia S, Oddis CV, Sato S, et al. Antimelanoma Differentiation-associated Gene 5 Antibody: Expanding the Clinical Spectrum in North American Patients with Dermatomyositis. J Rheumatol 2017;44:319-25. [Crossref] [PubMed]
70. Li S, Sun Y, Shao C, et al. Prognosis of adult idiopathic inflammatory myopathy-associated interstitial lung disease: a retrospective study of 679 adult cases. Rheumatology (Oxford) 2021;60:1195-204. [Crossref] [PubMed]
71. Kurasawa K, Arai S, Namiki Y, et al. Tofacitinib for refractory interstitial lung diseases in anti-melanoma differentiation-associated 5 gene antibody-positive dermatomyositis. Rheumatology (Oxford) 2018;57:2114-9. [Crossref] [PubMed]
72. George PM, Spagnolo P, Kreuter M, et al. Progressive fibrosing interstitial lung disease: clinical uncertainties, consensus recommendations, and research priorities. Lancet Respir Med 2020;8:925-34. [Crossref] [PubMed]
73. Motegi SI, Sekiguchi A, Toki S, et al. Clinical features and poor prognostic factors of anti-melanoma differentiation-associated gene 5 antibody-positive dermatomyositis with rapid progressive interstitial lung disease. Eur J Dermatol 2019;29:511-7. [Crossref] [PubMed]
74. Selva-O'Callaghan A, Romero-Bueno F, Trallero-Araguás E, et al. Pharmacologic Treatment of Anti-MDA5 Rapidly Progressive Interstitial Lung Disease. Curr Treatm Opt Rheumatol 2021;7:319-33. [Crossref] [PubMed]
75. Saito T, Mizobuchi M, Miwa Y, et al. Anti-MDA-5 antibody-positive clinically amyopathic dermatomyositis with rapidly progressive interstitial lung disease treated with therapeutic plasma exchange: A case series. J Clin Apher 2021;36:196-205. [Crossref] [PubMed]
76. Shirakashi M, Nakashima R, Tsuji H, et al. Efficacy of plasma exchange in anti-MDA5-positive dermatomyositis with interstitial lung disease under combined immunosuppressive treatment. Rheumatology (Oxford) 2020;59:3284-92. [Crossref] [PubMed]
77. Sasaki N, Nakagome Y, Kojima A, et al. Early Initiation of Plasma Exchange Therapy for Anti-MDA5(+)Dermatomyositis with Refractory Rapidly Progressive Interstitial Lung Disease. Intern Med 2024;63:213-9. [Crossref] [PubMed]
78. Abe Y, Kusaoi M, Tada K, et al. Successful treatment of anti-MDA5 antibody-positive refractory interstitial lung disease with plasma exchange therapy. Rheumatology (Oxford) 2020;59:767-71. [Crossref] [PubMed]
79. Kagawa H, Tsujino K, Yamamoto Y, et al. Acute lung injury after plasma exchange in a patient with anti-MDA5 antibody-positive, rapidly progressive, interstitial lung disease: A case report. Respir Med Case Rep 2020;29:101016. [Crossref] [PubMed]
80. Hamada-Ode K, Taniguchi Y, Kimata T, et al. High-dose intravenous immunoglobulin therapy for rapidly progressive interstitial pneumonitis accompanied by anti-melanoma differentiation-associated gene 5 antibody-positive amyopathic dermatomyositis. Eur J Rheumatol 2015;2:83-5. [Crossref] [PubMed]
81. Wang LM, Yang QH, Zhang L, et al. Intravenous immunoglobulin for interstitial lung diseases of anti-melanoma differentiation-associated gene 5-positive dermatomyositis. Rheumatology (Oxford) 2022;61:3704-10. [Crossref] [PubMed]
82. Crow J, Lindsley J, Cho SM, et al. Analgosedation in Critically Ill Adults Receiving Extracorporeal Membrane Oxygenation Support. ASAIO J 2022;68:1419-27. [Crossref] [PubMed]
83. Abidi E, El Nekidy WS, Atallah B, et al. Sustaining Life versus Altering Life-Saving Drugs: Insights to Explain the Paradoxical Effect of Extracorporeal Membrane Oxygenation on Drugs. J Clin Med 2023;12:3748. [Crossref] [PubMed]
84. Cheng V, Abdul-Aziz MH, Roberts JA, et al. Overcoming barriers to optimal drug dosing during ECMO in critically ill adult patients. Expert Opin Drug Metab Toxicol 2019;15:103-12. [Crossref] [PubMed]
85. Wan X, Bian T, Ye S, et al. Extracorporeal membrane oxygenation as a bridge vs. non-bridging for lung transplantation: A systematic review and meta-analysis. Clin Transplant 2021;35:e14157. [Crossref] [PubMed]