[Dermatomyositis].

Dermatomyositis (DM) is distinguished from other idiopathic inflammatory myopathies by the characteristic skin rashes, muscle pathology, and muscle symptoms. Five myositis-specific autoantibodies have been identified in DM, and the correlation between each antibody and the clinical picture is clear. Pathological analysis has also identified DM as a type I interferonopathy of the skeletal muscle. Consideration of treatment strategies requires careful evaluation of muscle strength, systemic inflammatory findings, muscle pathology, muscle imaging, and complications such as malignancy and interstitial lung disease. Corticosteroids are administered as first-line treatment, and immunosuppressive agents and intravenous immunoglobulins are employed as important second-line treatments. Some patients exhibit resistance to these therapies. Currently, treatment strategies for refractory cases are not well established, necessitating further development of treatment methods.

Successful Treatment of Ultrasound-confirmed Synovitis in Anti-MDA5 Antibody-positive Clinically Amyopathic Dermatomyositis with Corticosteroid Therapy.

Anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive clinically amyopathic dermatomyositis (CADM) is a subtype of dermatomyositis without severe myositis but with characteristic cutaneous manifestations and severe interstitial lung disease. Joint symptoms can occur in patients with anti-MDA5 antibody-positive CADM. However, the treatment strategy and utility of ultrasound for treating joint symptoms remain unknown. We herein report an 85-year-old man with anti-MDA5 antibody-positive CADM who presented with ultrasound-confirmed synovitis that improved with medium-dose corticosteroid therapy.

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.

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.

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.

[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.

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.

Local injection of infliximab into calcinosis lesions in patients with juvenile dermatomyositis (JDM): a clinical trial.

BACKGROUND: Juvenile Dermatomyositis (JDM) is a rare autoimmune disorder that primarily affects muscles and skin. One of the severe complications associated with JDM is calcinosis, and treating this condition presents significant challenges. This study aimed to evaluate the efficacy and safety of local injection of infliximab into calcinosis lesions in patients with JDM. METHODS: In this clinical trial, five patients diagnosed with JDM and calcinosis lesions were enrolled. The primary treatment consisted of weekly infliximab injections for 16 weeks, targeting all four sides of each lesion. Lesion dimensions, including length and width, were documented and monitored weekly. Before the intervention, patients underwent radiographic imaging. After the final injection in week 16, a follow-up radiographic assessment was performed. Data were analyzed using the Generalized Estimating Equation (GEE) method. RESULTS: The lesions' size significantly decreased in both length and width during each visit. On average, the lesion length reduced by 2.66%, and the width shrank by 3.32% per visit. Based on radiographic findings, the average length and width of lesions at the initial visit were 12.09 ± 5.05 mm (range: 6.00-25.50 mm) and 6.35 ± 3.00 mm (range: 2.00-16.00 mm), respectively. The average length and width at the last visit were 5.59 ± 7.05 mm (range: 0-23.00 mm) and 3.41 ± 4.05 mm (range: 0-13.00 mm), respectively. No specific side effects related to the treatment were reported. CONCLUSIONS: The results suggest that the direct administration of infliximab into the calcinosis lesions of patients with JDM could be a safe and effective treatment approach. TRIAL REGISTRATION: Name of the registry: The effect of infliximab injection into calcinosis lesions on patients with juvenile dermatomyositis (JDM), Trial registration number: IRCT20210808052107N1, Registration date: 2022-07-22, URL of trial registry record: https://en.irct.ir/trial/58329 .

Aggressive multi-combination therapy for anti-MDA5 antibody-positive dermatomyositis-rapidly progressive interstitial lung disease.

OBJECTIVES: To elucidate the efficacy and safety of aggressive multi-combination therapy with mycophenolate mofetil, rituximab, and plasma exchange or polymyxin B immobilized fiber column direct hemoperfusion followed by conventional therapy with corticosteroids, calcineurin inhibitors, and intravenous pulse cyclophosphamide in patients with rapidly progressive interstitial lung disease (RPILD) with anti-melanoma differentiation-associated gene 5 (MDA5)-antibody-positive dermatomyositis (DM). METHODS: A total of 23 patients with anti-MDA5 antibody-positive DM-RPILD were enrolled, with nine patients in Group A (treated conventionally before March 2015) and 14 patients in Group B (received aggressive treatment after April 2015). RESULTS: Pretreatment severity of interstitial lung disease (ILD) did not differ between the two groups. However, Group B exhibited a higher cumulative survival rate at 48 weeks than Group A (64.3% vs. 33.3%). The corticosteroid dose, divided by the initial dose at 3 months and 12 months, was significantly lower in Group B than in Group A (p = .046 and .026, respectively). Among the ILD-related deaths in Group B, there was a tendency toward a higher proportion of males and more severe ILD. The incidence of infection did not differ between the groups, but leukopenia was more common in Group B. CONCLUSION: This aggressive multi-combination therapy may improve the survival outcome of patients with anti-MDA5 antibody-positive DM-RPILD. However, careful management of complications, such as opportunistic infections and leukopenia, is essential. Future refinement through longitudinal investigations tracking the long-term efficacy, safety, and cost-effectiveness of this treatment strategy is needed.

Anti-melanoma Differentiation-associated Gene 5 Antibody-positive Dermatomyositis Presenting as Refractory Gingivitis at the First Clinical Manifestation.

We herein report a case of melanoma differentiation-associated gene 5 (MDA5) antibody-positive dermatomyositis that developed in a patient with refractory gingivitis. The diagnosis of anti-MDA5 antibody-positive dermatomyositis was made based on a characteristic skin rash, weakness of proximal muscles, interstitial pneumonia, and positivity for anti-MDA5 antibody. The patient was started on triple therapy with high-dose prednisolone, tacrolimus, and intravenous cyclophosphamide. After treatment, the refractory gingivitis disappeared, and the other skin rash and interstitial lung disease also improved. In the diagnosis and treatment of anti-MDA5 antibody-positive dermatomyositis, it is necessary to pay attention to the intraoral findings, including the gingiva.

Biologic drugs in the treatment of juvenile dermatomyositis: a literature review.

There is no clear consensus in the literature regarding the choice of biologic therapies and efficacy in juvenile dermatomyositis (JDM). In this review, we aimed to examine previous studies regarding biologic drug use in JDM patients. We screened MEDLINE and Scopus for articles involving JDM patients treated with biologic drugs. We identified 74 articles describing 495 JDM patients treated with biologic drugs (538 biologic treatments) during our literature search. The median (min-max) age of these patients was 9.8 (1-17) years (F/M:1.8). The most frequently used biologic drugs were rituximab (RTX, 50%) and tumor necrosis factor (TNF) inhibitors (34.8%). In a few cases, abatacept (4.3%), anti-interleukin-1 agents (0.9%), tocilizumab (0.9%), bortezomib (0.4%), ustekinumab (0.2%), eculizumab (0.2%), and golimumab (0.2%) were used. RTX was most frequently preferred in patients with severe skin involvement (46.3%). Improvement with RTX was obtained in 60.1% of RTX treatments. Infliximab was most frequently preferred in calcinosis (43.3%), while adalimumab in skin involvement (50%) and etanercept in resistant/recurrent diseases (80%). Improvement was achieved in 44.4% of anti-TNF treatments. Adverse events were observed in 46.8% (58/124) of all treatments. Our results suggest that biologic agents may be a promising alternative for the treatment of particularly resistant JDM cases. Controlled studies are required to provide higher level of evidence for the timing of biologic use in JDM treatment. Key Points • There is no consensus on the choice and efficacy of biologic therapies in JDM. • RTX and TNF inhibitors are the most commonly used biologic drugs. • Biologics were especially preferred in severe skin involvement, calcinosis, and resistant diseases.