A case of microscopic polyangiitis with interstitial pneumonia after coronavirus disease-2019 infection, evidenced by positivity for multiple autoantibodies.

Anti-neutrophil cytoplasmic antibody-associated vasculitis is triggered by infection, dust exposure, and drugs. A 73-year-old male presented with dyspnea. Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection was confirmed upon admission. Exacerbation of interstitial pneumonia and renal dysfunction were observed. Analysis revealed positivity for myeloperoxidase-anti-neutrophil cytoplasmic antibody, other anti-aminoacyl transfer RNA synthetase antibodies, and anti-melanoma differentiation-associated gene 5. Renal biopsy confirmed crescentic glomerulonephritis, leading to the diagnosis of microscopic polyangiitis. Combination therapy with prednisolone and cyclophosphamide was initiated, resulting in improved respiratory and renal failure. There is a potential association between SARS-CoV-2 infection and the onset of autoimmune diseases.

Successful pain control with add-on methadone for refractory neuropathic pain due to radiation necrosis in pontine metastatic lesion: a case report.

BACKGROUND: Central pain, characterized by neuropathic pain, can manifest due to injury to the superior spinothalamic tract. The brainstem includes sensory and motor pathways as well as nuclei of the cranial nerves, and therefore cancer metastasis in the region requires early intervention. Although stereotactic radiosurgery (SRS) is commonly employed for the treatment of brain metastasis, it poses risks of late complications like radiation necrosis (RN). RN exacerbates the progression of brain lesions within the irradiated area, and in the brainstem, it can damage multiple nerves, including the superior spinothalamic tract. Central neuropathic pain is often intractable and empirically managed with a combination of conventional drugs, such as serotonin-norepinephrine reuptake inhibitors (SNRIs) and anticonvulsants. However, their efficacy is often limited, leading to a decline in performance status (PS) and quality of life (QOL). CASE PRESENTATION: We present the case of a 53-year-old man diagnosed with stage IV lung cancer, referred to our palliative care team for managing severe central pain resulting from SRS-related RN in the pons. Despite administration of opioids, including oxycodone and hydromorphone, and adjuvant analgesics, the patient continued to require frequent use of immediate-release opioids. The addition of methadone alone proved successful in achieving optimal pain control. CONCLUSIONS: Provided that RN in the brainstem can lead to intractable neuropathic pain, it is advisable to avoid SRS for brainstem metastasis when possible. Add-on methadone should be considered as a viable pain management medication for patients experiencing unresolved central pain.

Current challenges in the diagnosis and management of idiopathic pulmonary fibrosis in Japan.

Idiopathic pulmonary fibrosis (IPF) is the archetypal interstitial lung disease. It is a chronic progressive condition that is challenging to manage as the clinical course of the disease is often difficult to predict. The prevalence of IPF is rising globally and in Japan, where it is estimated to affect 27 individuals per 100,000 of the population. Greater patient numbers and the poor prognosis associated with IPF diagnosis mean that there is a growing need for disease management approaches that can slow or even reverse disease progression and improve survival. Considerable progress has been made in recent years, with the approval of two antifibrotic therapies for IPF (pirfenidone and nintedanib), the availability of Japanese treatment guidelines, and the creation of global and Japanese disease registries. Despite this, significant unmet needs remain with respect to the diagnosis, treatment, and management of this complex disease. Each of these challenges will be discussed in this review, including making a timely and differential diagnosis of IPF, uptake and adherence to antifibrotic therapy, patient access to pulmonary rehabilitation, lung transplantation and palliative care, and optimal strategies for monitoring and staging disease progression, with a particular focus on the status in Japan. In addition, the review will reflect upon how ongoing research, clinical trials of novel therapies, and technologic advancements (including artificial intelligence, biomarkers, and genomic classification) may help address these challenges in the future.

Identification and management of interstitial lung disease associated with systemic sclerosis (SSc-ILD), rheumatoid arthritis (RA-ILD), and polymyositis/dermatomyositis (PM/DM-ILD): development of expert consensus-based clinical algorithms.

BACKGROUND: Clinical guidance on the identification and management of connective tissue disease-associated interstitial lung disease (CTD-ILD) is needed for optimal clinical practice. We aimed to develop clinical algorithms for identifying and managing three common CTD-ILDs: those associated with systemic sclerosis (SSc-ILD), rheumatoid arthritis (RA-ILD), and polymyositis/dermatomyositis (PM/DM-ILD). RESEARCH DESIGN AND METHODS: Meetings were held October-November 2023 to create consensus-based algorithms for identifying and managing SSc-ILD, RA-ILD, and PM/DM-ILD in clinical practice, based on expert consensus statements for identification and management of CTD-ILD previously derived from a Delphi process. RESULTS: We developed clinical algorithms for SSc-ILD, RA-ILD, and PM/DM-ILD that highlight both commonalities and differences in the identification and management of these CTD-ILDs. Importantly, ILD should be suspected in patients with SSc, RA, or PM/DM who have respiratory symptoms. Chest high-resolution computed tomography has utility for screening, diagnosis and assessment of severity. Furthermore, regular follow-up and multidisciplinary management are important. Disease-specific considerations include unique risk factors such as anti-topoisomerase I antibodies in SSc-ILD, high-titer cyclic citrullinated peptide antibodies in RA, anti-aminoacyl tRNA synthetase antibodies in PM/DM, and anti-melanoma differentiation-associated gene 5 antibody in DM. CONCLUSIONS: These algorithms may help physicians to identify and manage patients with SSc-ILD, RA-ILD, or PM/DM-ILD.

Japanese guidelines for the treatment of idiopathic pulmonary fibrosis 2023:Revised edition.

Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease with a poor prognosis and an unknown cause that generally progresses to pulmonary fibrosis and leads to irreversible tissue alteration. The "Guidelines for the treatment of idiopathic pulmonary fibrosis 2017," specializing in the treatment of IPF for the first time in Japan and presenting evidence-based standard treatment methods suited to the state of affairs in Japan, was published in 2017, in line with the 2014 version of "Formulation procedure for Minds Clinical Practice Guidelines." Because new evidence had accumulated, we formulated the "Guidelines for the treatment of Idiopathic Pulmonary Fibrosis 2023 (revised 2nd edition)." While keeping the revision consistent with the ATS/ERS/JRS/ALAT IPF treatment guidelines, new clinical questions (CQs) on pulmonary hypertension were added to the chronic stage, in addition to acute exacerbation and comorbid lung cancer, which greatly affect the prognosis but are not described in the ATS/ERS/JRS/ALAT IPF guidelines. Regarding the advanced stages, we additionally created expert consensus-based advice for palliative care and lung transplantation. The number of CQs increased from 17 in the first edition to 24. It is important that these guidelines be used not only by respiratory specialists but also by general practitioners, patients, and their families; therefore, we plan to revise them appropriately in line with ever-advancing medical progress.

Clinical practice guidelines of the Japan Research Committee of the Ministry of Health, Labour, and Welfare for Intractable Vasculitis for the management of microscopic polyangiitis and granulomatosis with polyangiitis: The 2023 update - secondary publication.

OBJECTIVE: To revise the 2017 clinical practice guidelines (CPG) for the management of microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) to reflect advancements in the field. METHODS: Similar to the 2017 CPG, the Grading of Recommendations, Assessment, Development, and Evaluation system was adopted for this revision. The intended users of this CPG include patients diagnosed with MPA or GPA in Japan and their families and healthcare professionals, including specialists and non-specialists. Based on a scoping review, four clinical questions (CQs) of the 2017 guidelines were modified, and six new CQs were added. RESULTS: We suggest a combination of glucocorticoid and cyclophosphamide or rituximab for remission induction therapy. In cases where cyclophosphamide or rituximab is used, we suggest the use of avacopan over high-dose glucocorticoid. Furthermore, we suggest against the use of plasma exchange in addition to the standard treatment in severe cases of MPA/GPA. Finally, we suggest the use of glucocorticoid and rituximab over glucocorticoid and azathioprine for remission maintenance therapy. CONCLUSIONS: The recommendations have been updated based on patient preference, certainty of evidence, benefit and risk balance, and cost.

Prolonged paradoxical reaction requiring over 5 years of corticosteroid administration in a patient with severe tuberculous meningitis.

Tuberculous meningitis (TBM) is a rare disease in low-incidence countries like Japan, where general physicians have fewer experience with TBM. Despite its proper treatment and early improvement of the condition, TBM often causes paradoxical reactions (PRs), which can lead to severe complications such as stroke. As PRs in the brain are difficult to detect without regular neuroimaging surveillance and have a later onset than in other organs, delayed treatment can be fatal. We report a case of a 54-year-old, human immunodeficiency virus (HIV)-negative man who presented with TBM and miliary tuberculosis (TB) in an unconscious state. Standard anti-tuberculous therapy with adjunctive systemic high-dose dexamethasone brought rapid clinical and microbiological improvement, which allowed the dexamethasone to be tapered. However, he developed cerebral infarction with left hemiplegia due to a TBM-related PR five months after admission. Therefore, the initial high-dose dexamethasone was again added to the anti-tuberculous drugs, achieving the significant effects on the PR-related lesions. Anti-tuberculous drugs had been administered for 3 years and the dexamethasone was carefully tapered. Nevertheless, enlargement of PR-related lesions in the brain recurred 5 years later. Accordingly, the dose of corticosteroid was again increased, resulting in resolving the lesions. It is important to note that severe TBM may cause prolonged PRs, which require a long-term neuroimaging follow-up and anti-inflammatory drugs for the successful management of the TBM-related PR.

Evaluation of Ministry of Health, Labour and Welfare diagnostic criteria for antineutrophil cytoplasmic antibody-associated vasculitis compared to ACR/EULAR 2022 classification criteria.

OBJECTIVE: This study aimed to evaluate the Ministry of Health, Labour and Welfare (MHLW) diagnostic criteria for antineutrophil cytoplasmic antibody-associated vasculitis compared to the new American College of Rheumatology/European Alliance of Associations for Rheumatology 2022 criteria. METHODS: Two nationwide cohort studies were used, and participants were categorised as having eosinophilic granulomatosis with polyangiitis, granulomatosis with polyangiitis (GPA), or microscopic polyangiitis (MPA) according to the American College of Rheumatology/European Alliance of Associations for Rheumatology 2022 and MHLW criteria. RESULTS: Of the entire patient population, only 10 (2.1%) were unclassifiable according to the MHLW probable criteria, while a significant number of patients (71.3%) met at least two criteria. The MHLW probable criteria for MPA had some challenges in differentiating between MPA and eosinophilic granulomatosis with polyangiitis, and the same was true for MHLW probable criteria for GPA in differentiating MPA from GPA. Nevertheless, improved classification results were obtained when the MHLW probable criteria were applied in the order of eosinophilic granulomatosis with polyangiitis, MPA, and GPA. CONCLUSIONS: The application of MHLW criteria could categorise a substantial number of patients with antineutrophil cytoplasmic antibody-associated vasculitis into one of the three antineutrophil cytoplasmic antibody-associated vasculitis diseases. The classification was in accordance with the American College of Rheumatology/European Alliance of Associations for Rheumatology 2022 criteria when considering the order of application.

Prevalence of systemic and local risk factors for pulmonary non-tuberculous mycobacterial disease in Japan: a single-institution study.

Objective: To identify the prevalence of risk factors for pulmonary non-tuberculous mycobacterial (NTM) disease in a Japanese population. Patients and Methods: We reviewed 337 consecutive Japanese patients (210 women) with pulmonary NTM disease, including 225 patients with Mycobacterium avium complex (MAC) disease (95.8%) at our hospital during 2006-2017. We calculated the prevalence of risk factors reported in Western countries among mycobacterial species. Results: Pulmonary MAC disease cases comprised 78.2% of pulmonary NTM patients in their 40s, increasing to 100% at age ≥80 years. Body mass index (BMI) was <18.5 in approximately 40% of patients, which was significantly higher than the prevalence of underweight in the Japanese population. The percentage of male heavy smokers (Brinkman index ≥600) was 58.2% of pulmonary NTM disease and was high for all mycobacterial species. In pulmonary MAC disease, systemic factors were observed in the order of malignant tumors (other than lung cancer), diabetes, rheumatoid arthritis, and tuberculosis. Local factors were observed in the order of bronchiectasis, chronic obstructive pulmonary disease, lung cancer, and bronchial asthma. Conclusion: The risk factors reported in Western countries were relatively highly prevalent among Japanese pulmonary NTM disease patients. This observation may help elucidate disease onset mechanisms.

Carboplatin and weekly paclitaxel in combination with bevacizumab for the treatment of advanced non-small cell lung cancer complicated by idiopathic interstitial pneumonias: A feasibility study.

BACKGROUND: Idiopathic interstitial pneumonias are an independent risk factor of lung cancer, and a chemotherapy-induced acute exacerbation is the most common lethal complication in Japanese patients. The safety and efficacy of carboplatin and weekly paclitaxel for the treatment of non-small cell lung cancer with idiopathic interstitial pneumonias has been previously reported in prospective studies. However, carboplatin + paclitaxel with bevacizumab is currently the standard therapy. We conducted a multicenter, phase II study to confirm the safety and efficacy of carboplatin + weekly paclitaxel + bevacizumab for the treatment of patients with lung cancer complicated by idiopathic interstitial pneumonias. METHODS: Chemotherapy-naïve patients with advanced-stage or patients with post-operative recurrent non-squamous non-small cell lung cancer complicated by idiopathic interstitial pneumonias were enrolled. Patients received carboplatin (area under the curve: 5.0) and bevacizumab (15 mg/kg) on day 1 and paclitaxel (100 mg/m2) on days 1, 8, and 15 of each 4-week cycle. RESULTS: Seventeen patients less than the predetermined number were enrolled and received a median of four treatment cycles (range: 1-6). One patient (5.9%; 95% confidence interval: 0.1-28.7%) had acute exacerbation of interstitial pneumonia related to the study treatment which improved after corticosteroid treatment. The overall response rate was 52.9%. The median progression-free survival, median survival time, and 1-year survival were 5.7 months, 12.9 months, and 52.9%, respectively. CONCLUSION: The addition of bevacizumab to carboplatin and weekly paclitaxel might be safe and effective for the treatment of advanced non-small cell lung cancer complicated by idiopathic interstitial pneumonias. CLINICAL TRIAL REGISTRATION NUMBER: UMIN000008189.

Identification and management of connective tissue disease-associated interstitial lung disease: evidence-based Japanese consensus statements.

BACKGROUND: Interstitial lung disease (ILD) is a common complication of connective tissue diseases (CTD), but there are few clinical trials to guide disease management. We aimed to develop expert consensus statements and an algorithm for CTD-ILD management. RESEARCH DESIGN AND METHODS: Based on a targeted literature review, we developed 109 statements on managing CTD-ILD across six domains. We used a modified Delphi process to survey 22 physicians in Japan involved in managing CTD-ILD (specialists in pulmonology, rheumatology, pathology, and radiology). These panelists participated in two rounds of web-based survey to establish consensus statements, which were used to define an algorithm. Consensus was defined as a mean value ≥70 on a scale of 0 (strong disagreement) to 100 (strong agreement). RESULTS: Between May-August 2022, consensus was reached on 93 statements on CTD-ILD management. The most important consensus statements included screening CTD patients for ILD (typically with high-resolution computed tomography), using imaging, pulmonary function testing and serum biomarkers for diagnosis and severity assessment, regularly following up patients, and multidisciplinary management of CTD-ILD. Consensus statements were interpreted into an algorithm for clinical guidance. CONCLUSIONS: Using the Delphi process, we have developed consensus statements and an algorithm to guide clinical decision-making for CTD-ILD.

Validation of new ACR/EULAR 2022 classification criteria for anti-neutrophil cytoplasmic antibody-associated vasculitis.

OBJECTIVE: The objective of this study was to compare the American College of Rheumatology/European Alliance of Associations for Rheumatology 2022 criteria with the previous classification algorithm for anti-neutrophil cytoplasmic antibody-associated vasculitis. METHODS: We used data from two nationwide, prospective, inception cohort studies. The enrolled patients were classified as having eosinophilic granulomatosis with polyangiitis (EGPA), granulomatosis with polyangiitis (GPA), or microscopic polyangiitis (MPA) according to the new criteria; these criteria were compared with Watts' algorithm. RESULTS: Among 477 patients, 10.7%, 9.9%, and 75.6% were classified as having EGPA, GPA, and MPA, respectively; 6.1% were unclassifiable. Three patients met both the EGPA and MPA criteria, and eight patients met both the GPA and MPA criteria. Of 78 patients with GPA classified using Watts' algorithm, 27 (34.6%) patients were reclassified as having MPA. Ear, nose, and throat involvement was significantly less frequent in patients reclassified as having MPA than in those reclassified as having GPA. Of 73 patients unclassifiable using Watts' algorithm, 62 were reclassified as having MPA. All patients reclassified as having MPA were myeloperoxidase-anti-neutrophil cytoplasmic antibody positive, and 46 had interstitial lung disease. CONCLUSION: Although the American College of Rheumatology/European Alliance of Associations for Rheumatology 2022 criteria cause overlapping multiple criteria fulfilments in some patients, those items contribute to classifying unclassifiable patients using Watts' algorithm into MPA.

Concordance between practice and published evidence in the management of ANCA-associated vasculitis in Japan: A cross-sectional web-questionnaire survey.

OBJECTIVES: We conducted a descriptive study of the physicians' evidence-practice gap for adults covered by the 2017 clinical practice guidelines for the management of antineutrophil cytoplasmic antibody-associated vasculitis in Japan. METHODS: This web-based survey, conducted between January and February 2021, involved physicians who had treated at least five patients in the preceding year at a regional core hospital. The outcome was the physicians' experience in treating patients with microscopic polyangiitis or granulomatosis with polyangiitis [prevalence with 95% confidence intervals (CIs)], defined as treating at least 60% of their patients with the recommended therapy during the year. A modified Poisson regression analysis was performed to explore the factors associated with concordance. RESULTS: The 202 participants included 49 pulmonologists, 65 nephrologists, 61 rheumatologists, and other physicians. The concordance was 31.5% (95% CI, 25.1-38.5) of physicians who used cyclophosphamide or rituximab for the induction of remission. Rheumatology showed the highest concordance with published evidence (risk ratio = 2.4; 95% CI, 1.10-5.22, p = .03). CONCLUSIONS: These results suggest an evidence-practice gap, which varies substantially among subspecialties. Further studies and a new promotional initiative are necessary to close this gap in clinical practice.

Design and rationale of the Japanese Idiopathic Interstitial Pneumonias (JIPS) Registry.

BACKGROUND: Numerous studies investigated patients with IPF; however, only a few examined patients with idiopathic interstitial pneumonias (IIPs). METHODS: The Japanese Idiopathic Interstitial Pneumonias (JIPS) Registry, which was initiated in December 2016, is a multicenter prospective observational study of patients newly diagnosed with IIPs from 86 facilities treating ILDs. The plan is to enroll more than 600 new patients during the 2-year enrolment period and to follow their progress for 3 years after the last case enrolment. If additional consent is obtained, the study will continue for another 2 years. Research questions mainly focus on identifying the frequency by IIP classification, patient background, and diagnostic methods during enrolment, survival, acute exacerbation rate, changes in high-resolution CT imaging, forced vital capacity, and interstitial pneumonia markers over time. Other research questions, including those regarding disease behavior in patients with progressive fibrosing-ILD and new biomarkers associated with genetic predispositions, will be investigated. DISCUSSION: The JIPS Registry will provide a comprehensive description of the disease progression, prognosis, treatment status, new biomarkers, and validity of guidelines and central multidisciplinary decisions for IPF and similar diseases that can be differentiated from IPF among IIPs. ETHICS AND DISSEMINATION: Ethical approval was obtained from the institutional review board of Kanagawa Cardiovascular and Respiratory Center (KCRC-16-0005), and that of Jichi Medical University approved the biobank part (I18-005). Results will be published in peer-reviewed journals and will be presented at national and international conferences. TRIAL REGISTRATION: ClinTrials.gov Registry (NCT03041623, first posted on February 3, 2017).

Respiratory lesions in IgG4-related disease: classification using 2019 American College of Rheumatology/European League Against Rheumatism criteria.

In this study, ILDs involving IgG4-positive plasma cell infiltration were classified using the 2019 ACR/EULAR criteria. Most IgG4-positive interstitial pneumonia cases were excluded, suggesting the need for a unique treatment strategy. https://bit.ly/38GiUJM.

Virulent Pseudomonas aeruginosa pneumonia in an immunocompetent adult associated with a home whirlpool bath: A case report.

We present a case of life-threatening pneumonia caused by Pseudomonas aeruginosa (P. aeruginosa) in a healthy 67-year-old man. Rapid disseminated infection resulted in the right hemorrhagic pneumonia and bacteremia. Antimicrobial therapy had limited effects, radical pneumonectomy eventually resolved the prolonged infection. Concurrently, we explored the environmental factors responsible for fulminant P. aeruginosa infection. Multi-locus sequence typing demonstrated that P. aeruginosa isolated from the patient was identical to that collected from home whirlpool bath by the common virulent factor gene. Massive inhalation of contaminated aerosol and pathogen virulence may have synergistically contributed to the severity in this case.

MPO-ANCA positive interstitial pneumonia: Current knowledge and future perspectives.

Although interstitial pneumonia is an important respiratory manifestation in microscopic polyangiitis (MPA), no studies have examined the detailed pathogenesis of interstitial pneumonia during the clinical course of MPA. In addition, it is considered that MPA develops at a certain incidence rate from myeloperoxidase (MPO)- antineutrophil cytoplasmic antibody (ANCA) positive interstitial pneumonia. However, there is a lack of consensus among pulmonologist and rheumatologist regarding whether MPO-ANCA positive interstitial pneumonia, which does not accompany other organ damage related to ANCA-associated vasculitis (AAV) other than interstitial pneumonia, should be included in AAV. In this review article, the clinical questions regarding MPO-ANCA positive interstitial pneumonia have been set, and evidence to date and problems to be solved in future are outlined.

Nation-wide survey of the treatment trend of microscopic polyangiitis and granulomatosis with polyangiitis in Japan using the Japanese Ministry of Health, Labour and Welfare Database.

OBJECTIVES: In Japan, clinical records of patients with intractable diseases, including microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA), are compiled into a database. This study aimed to understand the current treatment status and changes in treatment regimens from our previous survey. METHODS: Using data from 2012 and 2013, patients with new-onset MPA and GPA were extracted and analysed. RESULTS: We analysed 1278 MPA and 215 GPA patients. The average age was 71.7 and 62.7 years, respectively. Methylprednisolone pulse therapy was used in 51.2% of MPA patients and 40.5% of GPA patients; the initial prednisolone-equivalent glucocorticoid dose was 39.5 mg/day in MPA and 46.6 mg/day in GPA. Concomitant intravenous or oral cyclophosphamide (CY) was administered to 22.6% of MPA and 56.3% of GPA. Young age, bloody sputum, low serum creatinine, and high C-reactive protein levels were independently associated with CY use in MPA. Compliance with treatment protocol for Japanese patients with myeloperoxidase (MPO)-anti-neutrophilic cytoplasmic antibody-associated vasculitis study criteria or the 2011 clinical practice guidelines for rapidly progressive glomerulonephritis was 42.7% and 49.7%, respectively. CONCLUSIONS: MPA was more prevalent than GPA in the registry. Compared to patients with GPA, MPA patients were older and used CY less frequently. No apparent changes in treatment trends were observed from the previous survey.

Paradoxical Formation of a Pleuroparenchymal Fibroelastosis-like Lesion in the Chronic Course of Pulmonary Sarcoidosis.

We herein report the long-term changes in chest computed tomography (CT) findings from early sarcoidosis lesions to pleuroparenchymal fibroelastosis (PPFE)-like lesions in a 30-year-old man with granulomas on a transbronchial lung biopsy. Multiple bilateral micronodular and nodular opacities around the bronchovascular bundle in the upper lobes detected by chest CT in 2004 disappeared, but paradoxically, peripheral consolidations continued to grow at the periphery of the original lesions. Chest CT in 2017 confirmed the progression of bilateral shrinkage of the upper lobe, spread of peripheral consolidations and wedge-shaped opacities below the first rib, and bronchiectatic air bronchograms, confirming PPFE-like lesions.