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.

Sustained antitumor response to lenvatinib with weekend-off and alternate-day administration in chemotherapy-refractory thymic carcinoma: a case report.

Lenvatinib is a multitargeted kinase inhibitor and maintaining its dose intensity has been shown to be beneficial in patients with thyroid and hepatocellular carcinomas. However, most patients require lenvatinib interruption and dose reduction due to the high incidence of adverse events (AEs). Lenvatinib was recently approved in Japan for patients with unresectable thymic carcinoma; however, real-world evidence of its clinical benefit is limited. Here, we report the case of chemotherapy-refractory thymic carcinoma in a patient who was administered a starting dose of lenvatinib using a 5-day on/2-day off (weekend-off) protocol, followed by alternate-day administration after fatigue onset derived from overt or subclinical hypothyroidism. Consequently, the patient exhibited a durable response to lenvatinib, with a 17-month progression-free survival without any severe or intolerable AEs. The present case suggests that maintaining lenvatinib dose intensity using such alternative administration regimens contributes to favorable clinical outcomes in thymic carcinoma.

Clinical differences among patients with myeloperoxidase-antineutrophil cytoplasmic antibody-positive interstitial lung disease.

INTRODUCTION: Patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis and idiopathic interstitial lung diseases (IIPs) are positive for myeloperoxidase (MPO)-ANCA. MPO-ANCA-positive vasculitis mainly comprises microscopic polyangiitis (MPA) and unclassifiable vasculitis. These diseases are frequently complicated by interstitial lung disease (ILD). Few studies have reported the clinical differences between the subtypes of MPO-ANCA-positive ILD. Therefore, this study aimed to examine the clinical findings and courses of MPO-ANCA-positive ILD. METHOD: This retrospective study enrolled 100 patients with MPO-ANCA-positive ILD who were categorized into three groups: MPA (n = 44), unclassifiable vasculitis (n = 29), and IIP (n = 27). Our study compared the clinical findings and prognosis of these patients and analyzed the poor prognostic factors. Furthermore, we assessed the association between the patients with and without acute exacerbation of ILD (AE-ILD). RESULTS: Our study found clinical differences in serum markers, clinical symptoms, and treatment regimens among the three groups. ILD complications, as the main cause of death, differed among the three groups (P = 0.04). Patients with unclassifiable vasculitis showed higher survival rates than those with IIP (P = 0.046). Patients with AE-ILD showed fewer general symptoms (P = 0.02) and lower survival rates (P < 0.01) than those without AE-ILD. In multivariate analysis, AE-ILD development was a strong poor prognostic factor for MPO-ANCA-positive ILD. CONCLUSIONS: The subtypes of MPO-ANCA-positive ILD have different clinical features and prognoses. Patients who develop AE-ILD require careful evaluation of clinical courses. Key Points • In myeloperoxidase (MPO)-antineutrophil cytoplasmic antibody (ANCA)-positive interstitial lung disease (ILD), patients with unclassifiable vasculitis showed a better prognosis than those with idiopathic ILD.. • Development of acute exacerbation in ILD was a strong poor prognostic factor in patients with MPO-ANCA-positive ILD..

Durable response to afatinib rechallenge in a long-term survivor of non-small cell lung cancer harboring EGFR L858R and L747V mutations.

Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors are standard therapeutic agents for non-small cell lung cancer (NSCLC) patients with major EGFR mutations such as exon 19 deletions and a L858R mutation, whereas treatment strategies for cases with uncommon EGFR mutations remain to be fully established. Here, we report a long-term (≥20 years from initial diagnosis) NSCLC survivor carrying EGFR L858R and L747V mutations. The patient received gefitinib monotherapy, systemic chemotherapy/chemoimmunotherapy, and local consolidative therapies for oligometastatic lesions, and responded to afatinib rechallenge with a progression-free survival of 12 months. The current case suggests that afatinib is effective in NSCLC patients with EGFR L858R and L747V mutations and that a therapeutic approach combining appropriately timed systemic therapies with local consolidative therapies for oligometastatic lesions improves long-term survival.

Quantitative CT analysis of interstitial pneumonia in anti-melanoma differentiation-associated gene 5 antibody-positive dermatomyositis: a single center, retrospective study.

INTRODUCTION: This study aimed to assess the utility of quantitative high-resolution computed tomography (HRCT) for determining the clinical course of anti-melanoma differentiation-associated gene 5 antibody-positive dermatomyositis-associated interstitial lung disease (MDA5+ ILD). METHOD: This study retrospectively analyzed the data of 34 patients with MDA5+ ILD to determine the association between the clinical findings and extent of ILD via quantitative CT analysis at baseline and short-term follow-up. Quantified HRCT scores were evaluated as the lung severity score (LSS), percentage of opacity, and percentage of high opacity. RESULTS: Thirty-four patients underwent follow-up CT scans 35 (range: 14-78) days after diagnosis. Patients who died of rapidly progressive ILD had higher LSS (p < 0.01), percentage of opacity (p < 0.01), percentage of high opacity (p = 0.01), total ground-glass opacity score (p = 0.01), serum C-reactive protein (CRP) (p = 0.03), and alveolar-arterial oxygen difference (Aa-DO2) (p = 0.01) at follow-up than those who survived. Quantified HRCT scores correlated with serum CRP and Aa-DO2 levels at follow-up. LSS at follow-up (AUC = 0.844, p < 0.01) was the best predictor of death in MDA5+ ILD patients. Patients with an LSS of > 6.5 at follow-up had higher mortality than those with an LSS of ≤ 6.5, especially when receiving triple therapy. In multivariate analysis, an LSS of > 6.5 at follow-up was significantly associated with a poor outcome. CONCLUSIONS: Quantitative CT analysis of MDA5+ ILD is useful for the objective assessment of respiratory status and disease activity. Short-term HRCT evaluation, particularly LSS, is most important in predicting its clinical course during triple therapy. Key Points • Quantitative CT analysis plays an important role in evaluating the clinical course of anti-melanoma differentiation-associated gene 5 antibody-positive dermatomyositis-associated interstitial lung disease (MDA5+ ILD). • Quantified HRCT scores, particularly lung severity score, at short-term intervals from diagnosis can help to predict prognosis after triple therapy in MDA5+ ILD.

Influence of obesity in interstitial lung disease associated with anti-aminoacyl-tRNA synthetase antibodies.

BACKGROUND: Obesity is a major risk factor for developing various respiratory diseases. Patients with anti-aminoacyl tRNA synthetase (ARS) antibodies often have interstitial lung disease (ILD). The present study was conducted to evaluate the association between obesity and outcomes of anti-ARS antibody-related ILD (ARS-ILD). METHODS: We retrospectively investigated 58 patients with ARS-ILD and compared the clinical characteristics, treatment, and prognoses between obese (body mass index [BMI] ≥25 kg/m2) and nonobese (BMI <25 kg/m2) patients. Chest fat was quantified via computed tomography (CT). Thoracic subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) were measured at diagnosis and first relapse of ILD. RESULTS: Sixteen patients were obese. Obese patients had lower percentages of predicted diffusing capacity of the lungs for carbon monoxide and higher high-resolution CT scores and SAT and VAT indexes than did nonobese patients. The ILD relapse rate was higher in obese patients (P < 0.01), especially among those with high SAT indexes (P < 0.01). The SAT and VAT indexes increased significantly from diagnosis until first relapse. Among clinical parameters at first relapse, SAT and VAT indexes were correlated with serum Krebs von den Lungen-6 levels (r = 0.720, P = 0.008) and total ground-glass attenuation scores (r = 0.620, P = 0.024), respectively. CONCLUSIONS: Obesity and high SAT indexes are risk factors for ILD relapse in patients positive for anti-ARS antibodies. Evaluating and quantifying patients' chest fat on CT is important for predicting ILD relapse.