A case of autoimmune pulmonary alveolar proteinosis during the course of treatment of rapidly progressive interstitial pneumonia associated with anti-MDA5 antibody-positive dermatomyositis.

BACKGROUND: Autoimmune pulmonary alveolar proteinosis (APAP) is a diffuse lung disease that causes abnormal accumulation of lipoproteins in the alveoli; however, its pathogenesis remains unclear. Recently, APAP cases have been reported during the course of dermatomyositis. The combination of these two diseases may be coincidental; however, it may have been overlooked because differentiating APAP from a flare-up of interstitial pneumonia associated with dermatomyositis is challenging. This didactic case demonstrates the need for early APAP scrutiny. CASE PRESENTATION: A 50-year-old woman was diagnosed with anti-melanoma differentiation-associated gene 5 (anti-MDA5) antibody-positive dermatitis and interstitial pneumonia in April 2021. The patient was treated with corticosteroids, tacrolimus, and cyclophosphamide pulse therapy for interstitial pneumonia complicated by MDA5 antibody-positive dermatitis, which improved the symptoms and interstitial pneumonia. Eight months after the start of treatment, a new interstitial shadow appeared that worsened. Therefore, three additional courses of cyclophosphamide pulse therapy were administered; however, the respiratory symptoms and interstitial shadows did not improve. Respiratory failure progressed, and 14 months after treatment initiation, bronchoscopy revealed turbid alveolar lavage fluid, numerous foamy macrophages, and numerous periodic acid-Schiff-positive unstructured materials. Blood test results revealed high anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) antibody levels, leading to a diagnosis of APAP. The patient underwent whole-lung lavage, and the respiratory disturbance promptly improved. Anti-GM-CSF antibodies were measured from the cryopreserved serum samples collected at the time of diagnosis of anti-MDA5 antibody-positive dermatitis, and 10 months later, both values were significantly higher than normal. CONCLUSIONS: This is the first report of anti-MDA5 antibody-positive dermatomyositis complicated by interstitial pneumonia with APAP, which may develop during immunosuppressive therapy and be misdiagnosed as a re-exacerbation of interstitial pneumonia. In anti-MDA5 antibody-positive dermatomyositis, APAP comorbidity may have been overlooked, and early evaluation with bronchoalveolar lavage fluid and anti-GM-CSF antibody measurements should be considered, keeping the development of APAP in mind.

Reduced expressions of apoptosis-related proteins TRAIL, Bcl-2, and TNFR1 in NK cells of juvenile-onset systemic lupus erythematosus patients: relations with disease activity, nephritis, and neuropsychiatric involvement.

Background: Lupus pathogenesis is mainly ascribed to increased production and/or impaired clearance of dead cell debris. Although self-reactive T and B lymphocytes are critically linked to lupus development, neutrophils, monocytes, and natural killer (NK) cells have also been implicated. This study assessed apoptosis-related protein expressions in NK cells of patients with juvenile-onset systemic lupus erythematosus (jSLE) and relations to disease activity parameters, nephritis, and neuropsychiatric involvement. Methods: Thirty-six patients with jSLE, 13 juvenile dermatomyositis (JDM) inflammatory controls, and nine healthy controls had Fas, FasL, TRAIL, TNFR1, Bcl-2, Bax, Bim, and caspase-3 expressions in NK cells (CD3-CD16+CD56+) simultaneously determined by flow cytometry. Disease activity parameters included Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score, erythrocyte sedimentation rate, C-reactive protein level, anti-double strain DNA antibody level, complement fractions C3 and C4 levels. Results: Patients with jSLE had a profile of significantly reduced expression of TRAIL, Bcl-2, and TNFR1 proteins in NK cells when compared to healthy controls. Similar profile was observed in patients with jSLE with active disease, positive anti-dsDNA, nephritis, and without neuropsychiatric involvement. Patients with jSLE with positive anti-dsDNA also had reduced expression of Bax in NK cells when compared healthy controls and to those with negative anti-dsDNA. Yet, patients with jSLE with negative anti-dsDNA had reduced mean fluorescence intensity (MFI) of Bim in NK cells compared to healthy controls. Patients with jSLE with nephritis also had reduced MFI of Fas in NK cells when compared to those without nephritis. In addition, in patients with jSLE, the proportion of FasL-expressing NK cells directly correlated with the SLEDAI-2K score (rs = 0.6, p = 0.002) and inversely correlated with the C3 levels (rs = -0.5, p = 0.007). Moreover, patients with jSLE had increased NK cell percentage and caspase-3 protein expression in NK cells when compared to JDM controls. Conclusion: This study extends to NK cells an altered profile of TRAIL, Bcl-2, TNFR1, Fas, FasL, Bax, Bim, and caspase-3 proteins in patients with jSLE, particularly in those with active disease, positive anti-dsDNA, nephritis, and without neuropsychiatric involvement. This change in apoptosis-related protein expressions may contribute to the defective functions of NK cells and, consequently, to lupus development. The full clarification of the role of NK cells in jSLE pathogenesis may pave the way for new therapies like those of NK cell-based.

Autoimmunity against melanoma differentiation-associated gene 5 induces interstitial lung disease mimicking dermatomyositis in mice.

Anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive dermatomyositis (DM) is characterized by amyopathic DM with interstitial lung disease (ILD). Patients with anti-MDA5 antibody-associated ILD frequently develop rapidly progression and present high mortality rate in the acute phase. Here, we established a murine model of ILD mediated by autoimmunity against MDA5. Mice immunized with recombinant murine MDA5 whole protein, accompanied with complete Freund's adjuvant once a week for four times, developed MDA5-reactive T cells and anti-MDA5 antibodies. After acute lung injury induced by intranasal administration of polyinosinic-polycytidylic acid [poly (I:C)] mimicking viral infection, the MDA5-immunized mice developed fibrotic ILD representing prolonged respiratory inflammation accompanied by fibrotic changes 2 wk after poly (I:C)-administration, while the control mice had quickly and completely recovered from the respiratory inflammation. Treatment with anti-CD4 depleting antibody, but not anti-CD8 depleting antibody, suppressed the severity of MDA5-induced fibrotic ILD. Upregulation of interleukin (IL)-6 mRNA, which was temporarily observed in poly (I:C)-treated mice, was prolonged in MDA5-immunized mice. Treatment with anti-IL-6 receptor antibody ameliorated the MDA5-induced fibrotic ILD. These results suggested that autoimmunity against MDA5 exacerbates toll-like receptor 3-mediated acute lung injury, and prolongs inflammation resulting in the development of fibrotic ILD. IL-6 may play a key role initiating ILD in this model.

Elevated serum B-cell activator factor levels predict rapid progressive interstitial lung disease in anti-melanoma differentiation associated protein 5 antibody positive dermatomyositis.

BACKGROUND: Rapid progressive interstitial lung disease (RP-ILD) is the leading cause of anti-melanoma differentiation associated protein 5 antibody positive dermatomyositis (anti-MDA5+DM) related death. Elevated serum B-cell activating factor (BAFF) levels have been implicated in connective tissue diseases associated ILD. Here, we evaluate whether BAFF could be a prognostic biomarker for predicting RP-ILD in anti-MDA5+DM patients. METHODS: Serums were collected from 39 patients with anti-MDA5+DM (20 with RP-ILD and 19 with non-RP-ILD), 20 antisynthase syndrome (ASS) patients and 20 healthy controls (HC). BAFF concentration was measured by an enzyme-linked immunosorbent assay. RESULTS: Serum BAFF level was higher in anti-MDA5+DM patients than those in ASS patients and HC (3882.32 ± 1880.09 vs. 2540.89 ± 1403.04 and 2486.28 ± 767.97 pg/mL, p = 0.0056 and 0.0038, respectively). Within anti-MDA5+DM groups, RP-ILD patients exhibited higher BAFF concentration than non-RP-ILD group (4549.78 ± 1839.97 vs. 3297.28 ± 1794.69 pg/mL, p = 0.04). The BAFF concentration was positively correlated with levels of C-reactive protein (CRP), dehydrogenase (LDH) and cytokeratin (CK) in anti-MDA5+DM patients (r = 0.350, p = 0.035; r = 0.393, p = 0.016; r = 0.518, p = 0.001; respectively). The best cut-off value of BAFF concentration was 2971.5 pg/mL by ROC curve (AUC area = 0.690, p = 0.045) and BAFF > 2971.5 pg/mL was an independent risk factor for RP-ILD using multivariate analysis (OR = 9.389, 95% CI = 1.609-54.769; p = 0.013). CONCLUSIONS: Serum BAFF could be a useful prognostic biomarker for early detecting RP-ILD risk in anti-MDA5+DM patients.

Dynamic change in red cell distribution width as a predictor for short-time mortality in dermatomyositis-associated rapid progressive interstitial lung disease.

AIM: We aimed to explore a new and readily available practical marker for rapidly progressive interstitial lung disease (RP-ILD) and poor short-term outcomes in patients with idiopathic inflammatory myopathies (IIM). METHODS: A total of 1822 consecutive patients with IIM between 2009 and 2021 were evaluated retrospectively. All proven cases of naïve ILD with complete medical records were included. Red cell distribution width (RDW) values at the initial stage, 3 months and last follow-up were collected. The clinical characteristics and outcomes of the patients were recorded. RESULTS: We identified 532 patients with IIM with an average follow-up of 4 years. ILD prevalence was higher in patients of elevated RDW (p<0.001). The patients with ILD and elevated RDW had lower levels of PaO2/FiO2, FVC% and DLco% and a higher prevalence of RP-ILD than those with normal RDW (p<0.001). Prognostic analysis revealed that RDW was an independent risk factor for prognosis in patients with IIM-ILD (HR=2.9, p=0.03). Patients with dermatomyositis (DM) with RP-ILD with a change in RDW within 3 months (∆RDW-3) greater than 0 were more likely to die within 3 months. Moreover, the prevalence of ∆RDW-3>0 was higher in patients with RP-ILD and positive for anti-melanoma differentiation-associated gene 5 antibody who died within 3 months (87.5%) compared with those alive at 3 months (24.6%) (p<0.001). CONCLUSION: These findings suggest that repeated RDW assays could assist physicians in identifying patients with DM-ILD who were at a high risk of RP-ILD and death.

Baricitinib for anti-melanoma differentiation-associated protein 5 antibody-positive dermatomyositis-associated interstitial lung disease: a case series and literature review on Janus kinase inhibitors for the disease.

Anti-melanoma differentiation-associated protein 5 antibody-positive dermatomyositis (anti-MDA5-DM) is frequently complicated by progressive interstitial lung disease (ILD), the prognosis of which is poor, and management is a major challenge. We treated three patients with anti-MDA5-DM-associated ILD (anti-MDA5-DM-ILD) using the Janus kinase (JAK) inhibitor, baricitinib, which improved lung opacities and saved two patients. We reviewed 6 patients with anti-MDA5-DM-ILD who had been treated with tofacitinib at our institution. Five of the patients survived, although discontinuation of tofacitinib due to complications was frequently observed. In addition, a literature search of patients with anti-MDA5-DM-ILD who were treated with JAK inhibitors yielded 21 articles involving 79 cases. All patients except one were treated with tofacitinib, and the survival rate was 75.9%. Although not statistically confirmed, the deceased patients tended to be older and had higher ferritin levels. A total of 92 complications were observed, 11 of which resulted in JAK inhibitor discontinuation. Cytomegalovirus reactivation comprised a substantial percentage of all complications and of those patients who required JAK inhibitor discontinuation. Five cases with fatal infective complications were also observed. While tofacitinib has been proposed to be a therapeutic option for anti-MDA5-DM-ILD, other JAK inhibitors, including baricitinib, are a treatment option. Further investigation is warranted to optimize treatment of anti-MDA5-DM-ILD.

Anti-SAE dermatomyositis: clinical and histologic characteristics from a monocentric Italian cohort.

OBJECTIVES: Multiple myositis-specific antibodies have been identified, each associated with different clinical subsets of dermatomyositis (DM). Anti-SAE associated DM is considered the least studied subset. Our study aimed to evaluate the clinical and histological characteristics of DM patients with anti-SAE antibodies. As reference, patients with anti-Mi2 antibodies associated DM, representing a well-characterised subset, were analysed. METHODS: We recorded data from our DM cohort in the INflammatory MYositis REgistry (INMYRE). Patients were divided into two groups: those positive for anti-SAE and those positive for anti-Mi2 antibodies. Clinical characteristics, including skin, muscle, and extra-muscular involvements, were recorded. Available muscle biopsies were compared between the two groups. RESULTS: Of 92 DM patients, 10 (10.9%) were positive for anti-SAE and 17 (18.5%) for anti-Mi2. Anti-SAE positive DM patients showed classic DM findings but were characterised by a higher prevalence of skin itching (60% vs. 11.8%, p<0.01), shawl sign (40% vs. 5.9%, p<0.05) and lung involvement (30% vs. 0%, p<0.05) compared to anti-Mi2 positive patients. Furthermore, anti-SAE positive DM patients showed lower creatine kinase levels than those with anti-Mi2 (median [IQR]: 101 [58-647] vs. 1984 [974-3717], p<0.05) and a lower percentage of muscle fibre degeneration and necrosis (1.5%±1.7 vs. 5.9%±3.2, p<0.05) in muscle biopsies. No other differences were observed. CONCLUSIONS: Anti-SAE DM represents a disease subset characterised by classic cutaneous involvement often associated with itching, less severe muscle involvement, but potential pulmonary involvement that should always be investigated in these patients.

Treatment of myopathy and cutaneous ulcers in anti-MDA5-positive dermatomyositis with triple therapy.

Antimelanoma differentiation-associated protein 5 positive dermatomyositis (MDA5 DM) is a rare subtype of idiopathic inflammatory myopathy. There are limited data available regarding the cutaneous manifestations of MDA5 DM in the African American population. We presented the case of a male patient in his early 20s who presented with debilitating cutaneous ulceration and myopathy. Workup revealed interstitial lung disease (ILD) and positive MDA5 serology consistent with MDA5 DM. He made a remarkable recovery in terms of myopathy and cutaneous ulcerations with a multipronged regimen of prednisone, intravenous immunoglobulin and mycophenolate mofetil. However, there was a progression of ILD on this regimen which warranted use of rituximab.

Prevalence of hearing loss, tinnitus, vertigo and sudden deafness among patients with polymyositis and dermatomyositis.

Little is known about a possible association of autoimmune inner ear disease among patients diagnosed with polymyositis (PM)/dermatomyositis (DM). This study aimed to explore differences in the prevalence of inner ear symptoms among patients with and without PM/DM using a nationwide population-based dataset. Data for this study were retrieved from the Taiwan National Health Insurance Research Database. The study sample included 1622 patients diagnosed with PM/DM and 8109 propensity-score matched comparison patients without PM/DM. We performed multivariate logistic regressions to calculate odds ratios (ORs) and 95% confidence interval (CI) for tinnitus, hearing loss, sudden deafness, and vertigo among patients with PM/DM versus comparison patients. Chi-square tests showed statistically significant differences between patients with PM/DM and comparison patients in the prevalence of tinnitus (16.1% vs. 12.7%, p < 0.001), non-conductive hearing loss (9.2% vs. 6.8%, p < 0.001), and vertigo (14.4% vs. 11.1%, p < 0.001). The adjusted ORs for tinnitus, non-conductive hearing loss, and vertigo, respectively, were 1.332 (95% CI = 1.147-1.547), 1.399 (95% CI = 1.154-1.696), and 1.374 (95% CI = 1.173-1.611) for patients with PM/DM when compared to comparison patients. Our study finds that patients with PM/DM have higher prevalence rates of tinnitus, non-conductive hearing loss, and vertigo than comparison patients.

Diagnosis of multiple tuberculous muscle abscesses in a patient with systemic lupus erythematosus by metagenomic next-generation sequencing- a case report and literature review.

BACKGROUND: Early diagnosis of muscular tuberculosis (TB) without coexistent active skeletal involvement is often challenging because the disease is very rare and its clinical manifestation is nonspecific and misleading. To raise the awareness and emphasize early diagnosis of muscular TB, we present a case of multiple tuberculous muscle abscesses in a systemic lupus erythematosus (SLE) female, but without pulmonary tuberculosis (PTB), in order to increase awareness of and stress the need of early detection of muscular TB. CASE PRESENTATION: A 44-year-old woman with a 6-year history of SLE who had been treated with methylprednisolone for a long time complained of erythema on her trunk and extremities for five months, along with edema and myalgia for two months, and fever for one month. The patient was first misdiagnosed as SLE overlap dermatomyositis. However, an ultrasound-guided drainage of muscle abscesses revealed positive acid-fast staining combined with positive deoxyribonucleic acid fragment of Mycobacterium tuberculosis using metagenomic next-generation sequencing (mNGS). The patient was cured and released following standard anti-tuberculosis medication, local puncture drainage, and an intravitreal injection of streptomycin. Literature search found only 19 cases of tuberculous muscle abscesses occurring in the extremities reported from 1999 to 2023. CONCLUSIONS: Extrapulmonary TB with predominantly muscle involvement is rare and with no specific clinical presentation. Muscular tuberculosis may be disdiagnosed for dermatomyositis due to the high muscle enzyme levels, delaying diagnosis and treatment. mNGS technology is helpful in the early and rapid diagnosis of muscular TB. On the basis of traditional anti-tuberculosis treatment, an ultrasound-guided percutaneous puncture drainage and intracavitary injection of streptomycin for the treatment of tuberculous muscle abscess is easy to operate, safe and effective, which is worthy of clinical popularization and application.

FDG PET/CT Findings of a Small Cell Carcinoma of the Lung Presented as Diffuse Dermatomyositis.

ABSTRACT: Patients with dermatomyositis are prone to have occult malignancy. A previously healthy 68-year-old man with dermatomyositis underwent FDG PET/CT to detect possible malignancy of unknown origin. The images showed not only diffuse increased activity in the muscle, which was related to the known dermatomyositis, but also intense activity in the anterior chest with foci of abnormal activity throughout the body. Pathology examination confirmed small cell carcinoma of the lung with widespread metastases.

A bibliometric analysis of the research status and trends in studies on polymyositis and dermatomyositis with interstitial lung disease from 2000 to 2022 using Web of Science.

BACKGROUND: The main subtypes of idiopathic inflammatory myopathies (IIMs)-polymyositis (PM) and dermatomyositis (DM)-are often presented as interstitial lung disease (ILD) in clinical practice; therefore, many researchers have combined the three studies into PM/DM with ILD. METHODS: Using bibliometrics, the research status, progress, and hotspots of PM/DM with ILD between 2000 and 2022 were studied. Literature data on PM/DM with ILD were retrieved from the Web of Science (WoS) database for the research period. Visualization software, including VOSviewer, Pajek, CiteSpace, and Scimago Graphica were used for bibliometric analysis. RESULTS: A total of 1555 relevant articles were obtained, and the overall research in this field showed an increasing trend. Regarding contributing countries and venues, Japan published the most articles while Rheumatology was the most prolific journal. Regarding authors, the most published article was by Wang Guochun from Changchun University of Technology in China. Keyword analysis and cocited literature cluster analysis showed that diagnosis, classification, autoantibodies, antibodies, prognosis, complications, and treatment of PM/DM with ILD have been hot topics in this field recently. Moreover, our study shows that anti-mda5 antibody, mortality, gene 5 antibody, IIMs, double-blind, and prognostic factors, among others, may be new hot topics. CONCLUSION: This study found that research on PM/DM with ILD has increased over time, and scholars are paying more attention to this field. The development of new drugs for the management, treatment, and prevention of PM/DM with ILD is the primary task of researchers and a direction for future research in this field.

Comparative analysis of immunotherapy responses in small cell lung cancer patients with dermatomyositis.

Cancer-associated dermatomyositis (CAD), a paraneoplastic syndrome characterized by dermatomyositis (DM), frequently presents in association with small cell lung cancer (SCLC). Although the advent of immune checkpoint inhibitors (ICIs) has revolutionized cancer treatment, their efficacy and safety in patients with concurrent autoimmune diseases (AD) and malignancies remains uncertain. Several studies have suggested the safe administration of ICIs in patients with AD, indicating that successful cancer therapy can alleviate CAD symptoms. Conversely, other studies have raised concerns about the potential for ICIs to exacerbate AD flares or immune-related adverse events (irAEs). A comparative analysis of two cases from our institution emphasizes the variability in ICI responses among SCLC patients with CAD. One patient, previously reported as a case study, exhibited significant clinical improvement in DM symptoms after ICI administration, whereas the other developed severe exfoliative skin changes and experienced an unfavorable prognosis. This variability emphasizes the need for careful patient selection and close monitoring during ICI treatment. We hypothesized that overweight or obese individuals and those with severe initial skin lesions and elevated lactate dehydrogenase levels are more susceptible to developing irAEs following ICI therapy. Therefore, caution is advised when considering immunotherapy in these patients.

Concurrence of dermatomyositis and psoriasis: a case report and literature review.

Dermatomyositis (DM) is a type of inflammatory myopathy with unknown causes. It is characterized by distinct skin lesions, weakness in the muscles close to the body, and the potential to affect multiple organs. Additionally, it may be associated with the presence of malignancies. The development of DM is influenced by genetic susceptibility, autoimmune response, and various external factors like cancer, drugs, and infectious agents. Psoriasis is a chronic, recurring, inflammatory, and systemic condition. Scaly erythema or plaque is the typical skin manifestation. The etiology of psoriasis involves genetic, immune, environmental and other factors. It is uncommon for a patient to have both of these diseases simultaneously, although individuals with DM may occasionally exhibit symptoms similar to those of psoriasis. Our patient was diagnosed with psoriasis in his 50s because of scalp squamous plaques, but he did not receive standard treatment. Ten years later, he developed symptoms of muscle pain and limb weakness. He was diagnosed with psoriasis complicated with dermatomyositis in our department and received corresponding treatment. Moreover, we reviewed the relevant literature to evaluate similarities and differences in clinical manifestation and treatment to other cases.

Prognostic factors of fungal infection in anti-melanoma differentiation-associated gene 5 antibody-positive associated interstitial lung disease.

OBJECTIVE: To investigate the potential risk factors for mortality in fungal infection in anti-melanoma differentiation-associated gene 5 antibody-positive associated interstitial lung disease (MDA5-ILD). METHODS: Patients diagnosed with MDA5-ILD from April 2017 to November 2022 were included. The demographic data, laboratory examinations, therapeutic and follow-up information were recorded. Fungal infection diagnosis was established based on a combinations of host factors, clinical features and mycologic evidences. High-dose corticosteroid therapy was defined as the initial corticosteroid doses > 240mg/d. The primary endpoint was mortality. Potential factors for fungal infection occurrence and prognostic factors were analyzed using logistic regression analysis and Cox proportional hazards regression. RESULTS: In total, 121 patients with MDA5-ILD were included. During follow-up, 41 (33.9%) patients had suffered fungal infection and 39.0% (16/41) of whom had ever received high-dose corticosteroid therapy. The median interval from corticosteroid use to the occurrence of fungal infection was 29 (10-48) days. The mean survival time of patients with fungal infection was 234.32 ± 464.76 days. The mortality in MDA5-ILD with fungal infection was 85.4% (35/41), which was significantly higher than those without (85.4% VS 56.3%, P < 0.001). High-dose corticosteroid therapy (P = 0.049) was independent risk factor for fungal infection occurrence. Decreased serum albumin level (P = 0.024) and high-dose corticosteroid therapy (P = 0.008) were both associated with increased mortality in MDA5-ILD patients with fungal infection. CONCLUSION: Fungal infection is associated with an increased mortality in MDA5-ILD. The serum albumin level and corticosteroid dose should be taken into consideration when treating MDA5-ILD. Key Points • This study showed fungal infection is associated with an increased mortality in MDA5-ILD. In MDA5-ILD patients with fungal infection, the presence of decreased serum albumin level and high-dose corticosteroid therapy were identified as predictors for mortality.

Successful Treatment of Rapidly Progressive Interstitial Lung Disease in Juvenile Dermatomyositis.

Juvenile dermatomyositis (JDM) is a rare systemic autoimmune disease characterized by cutaneous findings, muscle inflammation, and vasculopathy. Patients with antimelanoma differentiation associated gene 5 (anti-MDA5) JDM may have subtle muscle weakness, absence of pathognomonic rashes, and more polyarthritis and ulcerative skin lesions when compared with other JDM subtypes. Although there is a known association of rapidly progressive interstitial lung disease (RP-ILD) in patients with anti-MDA5 dermatomyositis, few case reports describe this association in the pediatric literature. Even fewer reports describe successful treatment. We report an unusual case of RP-ILD in a pediatric patient with a hypomyopathic presentation complicated by prolonged intubation and pulmonary hemorrhage. A 4-year-old underweight female presented in respiratory distress and quickly progressed to severe hypoxic and hypercarbic respiratory failure requiring intubation. She experienced fatigue, intermittent fever, and transaminitis. The diagnosis was delayed because of recent travel history and a lack of typical cutaneous features of JDM, except a small erythematous papule on her antihelix. Her pulmonary hemorrhage and ear lesion prompted additional rheumatic workup. The myositis-specific antibody panel revealed high positive anti-MDA5 antibodies that prompted aggressive combination therapy with plasmapheresis, systemic steroids, inhibitors of Janus kinase, agents to deplete B-cells, and intravenous immunoglobulin. The patient responded well to treatment and was ultimately extubated and discharged. To our knowledge, this is the first thoroughly documented case of anti-MDA5 JDM with RP-ILD presenting with pulmonary hemorrhage and lacking typical cutaneous features. Early recognition of this highly fatal condition is important for improved prognosis.

Rapidly progressive interstitial lung disease risk prediction in anti-MDA5 positive dermatomyositis: the CROSS model.

Background: The prognosis of anti-melanoma differentiation-associated gene 5 positive dermatomyositis (anti-MDA5+DM) is poor and heterogeneous. Rapidly progressive interstitial lung disease (RP-ILD) is these patients' leading cause of death. We sought to develop prediction models for RP-ILD risk in anti-MDA5+DM patients. Methods: Patients with anti-MDA5+DM were enrolled in two cohorts: 170 patients from the southern region of Jiangsu province (discovery cohort) and 85 patients from the northern region of Jiangsu province (validation cohort). Cox proportional hazards models were used to identify risk factors of RP-ILD. RP-ILD risk prediction models were developed and validated by testing every independent prognostic risk factor derived from the Cox model. Results: There are no significant differences in baseline clinical parameters and prognosis between discovery and validation cohorts. Among all 255 anti-MDA5+DM patients, with a median follow-up of 12 months, the incidence of RP-ILD was 36.86%. Using the discovery cohort, four variables were included in the final risk prediction model for RP-ILD: C-reactive protein (CRP) levels, anti-Ro52 antibody positivity, short disease duration, and male sex. A point scoring system was used to classify anti-MDA5+DM patients into moderate, high, and very high risk of RP-ILD. After one-year follow-up, the incidence of RP-ILD in the very high risk group was 71.3% and 85.71%, significantly higher than those in the high-risk group (35.19%, 41.69%) and moderate-risk group (9.54%, 6.67%) in both cohorts. Conclusions: The CROSS model is an easy-to-use prediction classification system for RP-ILD risk in anti-MDA5+DM patients. It has great application prospect in disease management.

[A CASE OF CLINICALLY AMYOPATHIC DERMAMYOSITIS WITH INTERSTITIAL LUNG DISEASE SHOWING TWO DETERIORATIONS IN 4 YEARS].

We report the case of a 45-year-old man who was diagnosed with clinically amyopathic dermamyositis (CADM) and interstitial lung disease (ILD) after presenting with skin lesions typical of CADM and testing positive for anti-Melanoma Diferentiation-Associated gene 5 (anti-MDA5) anti-bodies. He was treated with a regimen including steroid pulse therapy, intravenous cyclophosphamide (IVCY), and calcineurin Inhibitor drug, which initially improved his ILD. However, three months post-treatment, the first deterioration of his conditions occurred, necessitating further administration of steroid pulse therapy and IVCY. After eight cycles of IVCY therapy, the serum levels of KL-6 and anti-MDA5 antibodies decreased, and reaching their lowest values. Nevertheless, two years and six months after the first observed deterioration, the second deterioration of his conditions occurred, leading to acute respiratory failure, treated again with steroid pulse therapy and IVCY. This treatment did not result in improvement of respiratory failure, therefore plasma exchange was attempted, which demonstrated a beneficial effect on the ILD for a short time. This case suggests that IVCY and plasma exchange might be effective therapeutic options for CADM with ILD.