Candida Pneumonia in a Young Vegan Man with Diabetic Ketoacidosis.

A 39-year-old vegan man was admitted with diabetic ketoacidosis. He had also developed pneumonia that was unresponsive to antibiotics. Based on bronchoscopy findings, the diagnosis of Candida pneumonia was made, and the pulmonary shadow disappeared rapidly after antifungal therapy. Candida pneumonia has been mostly reported in severely immunocompromised patients. This is a rare case of Candida pneumonia that was found in a young vegan man with diabetes mellitus (DM). Although malnutrition caused by DM or an unbalanced diet is often underestimated as a cause of immunodeficiency, these conditions can be risk factors for serious opportunistic infections, including Candida pneumonia.

Lenvatinib-refractory thymic mucinous carcinoma with PIK3CA mutation.

Mucinous adenocarcinoma, a very rare type of thymic carcinoma, is aggressive and has a poor prognosis. The optimal treatment for advanced thymic mucinous adenocarcinoma has not yet been established because of its rarity. An oral multi-tyrosine kinase inhibitor, lenvatinib, was approved for treatment of thymic carcinoma in March 2021 in Japan. However, to the best of our knowledge, there are no published reports concerning lenvatinib for thymic mucinous adenocarcinoma. Herein, we report a 39-year-old woman who presented with a 70 mm multilocular cystic tumor in her left anterior mediastinum and a massive pericardial effusion. We diagnosed a Masaoka stage IVb thymic mucinous adenocarcinoma with multiple metastases to the liver and bones, and pericardial dissemination on the basis of the pathologic findings on examination of a video-assisted thoracoscopic tumor biopsy and radiological examinations. She received paclitaxel-carboplatin-based chemotherapy, but developed a left cerebellar metastasis. Second-line chemotherapy with lenvatinib failed to suppress the tumor. She died of cancer progression 5 months after presentation. Here, we report what we believe to be the first case of a thymic mucinous adenocarcinoma treated with lenvatinib. Our patient's thymic mucinous adenocarcinoma was refractory to both cytotoxic chemotherapy and lenvatinib. Using next-generation sequencing, we identified phosphatidylinositol 3-kinase catalytic subunit alpha mutation in the tumor. We suspected an association between this mutation and resistance to lenvatinib. We therefore recommend performing next-generation sequencing when considering introduction of lenvatinib for thymic mucinous adenocarcinoma. A surgical procedure may be necessary for accurate diagnosis and genetic analysis of this histological tumor type.

Rituximab for the Treatment of Anti-glomerular Basement Membrane Disease with Isolated Diffuse Alveolar Hemorrhage.

Anti-glomerular basement membrane (GBM) disease with isolated diffuse alveolar hemorrhage (DAH) is rare. We herein report a 91-year-old man admitted with hypoxia and diagnosed with anti-GBM disease with DAH based on positive bronchoalveolar lavage and serum antibody test results. There was no renal involvement. Although remission was achieved using glucocorticoids and plasmapheresis, the patient experienced DAH relapse one week after the last plasmapheresis. Rituximab 375 mg/m2 was administered 4 times weekly; thereafter, DAH relapse was not observed, and the glucocorticoid dosage was tapered. Rituximab was thus effective in treating anti-GBM disease with isolated DAH in an extremely elderly patient.

Fragment size and dynamics of EGFR-mutated tumor-derived DNA provide prognostic information regarding EGFR-TKI efficacy in patients with EGFR-mutated NSCLC.

Circulating tumor DNA (ctDNA)-based next-generation sequencing (NGS) is a complementary and alternative test to tissue-based NGS. We performed NGS analysis of ctDNA samples collected from patients with EGFR-mutated non-small cell lung cancer (NSCLC) who received osimertinib; the samples were collected after second-line treatment, before osimertinib treatment, one week and one month after osimertinib treatment, and at the time of resistance formation. We examinedthe correlation with osimertinib efficacy. From January to December 2018, 34 patients with EGFR-mutated NSCLC harboring EGFR T790M mutations were enrolled, and a total of 132 peripheral blood samples were collected. The fragment sizes of EGFR-mutated ctDNAs were significantly shorter than that of their corresponding normal fragments. Osimertinib treatment of patients with shorter EGFR-mutated ctDNA fragments resulted in shorter progression-free survival (PFS). The disappearance time of EGFR-mutated fragment fractions and clonal evolution patterns (new driver mutation group, additional mutation group vs. attenuation group) were each associated with the PFS achieved with osimertinib treatment; however,multivariate analysis revealed that only shorter EGFR-mutated ctDNA fragments were associated with the PFS resulting from osimertinib treatment. EGFR-mutated ctDNA fragment size, time of disappearance of these fragments, and clonal evolution pattern were related to the effects of osimertinib. In particular, short EGFR-mutated ctDNA fragmentation may be closely related to osimertinib efficacy prediction.

Steroid treatment in patients with acute respiratory distress syndrome: a systematic review and network meta-analysis.

PURPOSE: Although the most recent systematic review and meta-analyses on acute respiratory distress syndrome (ARDS) have shown that the use of steroids decreases mortality in adult patients, its benefits and risks may differ depending on the type and dosage of the steroid. Therefore, we conducted a network meta-analysis (NMA) to compare the differences in the efficacy among different doses and types of steroids. METHODS: We searched MEDLINE, CENTRAL, ICHUSHI, ClinicalTrials.gov, and WHO ICTRP databases from the earliest records to March 2021 for randomized control trials, which compared steroids with placebo or conventional therapy for ARDS. Using the random-effects model, we compared various categories of steroids (high-dose methylprednisolone, low-dose methylprednisolone, hydrocortisone, dexamethasone, and no steroid) concerning hospital mortality, incidence of infection, and ventilator-free days (VFD). RESULTS: We analyzed nine studies involving adult patients (n = 1212). Although there were no significant differences between the groups in terms of the mortality and incidence of infection, the number of VFD were greater when using low-dose methylprednisolone than when not using any steroids (Mean difference: 6.06; 95% confidence intervals: [2.5, 10.5]). Moreover, the rank probability showed that low-dose methylprednisolone might be the optimal treatment, whereas using no steroid or high-dose methylprednisolone may be inferior to other treatments in terms of mortality, infection, and VFD. CONCLUSION: This NMA suggested that the effect of steroids on the outcome in patients with ARDS might depend on the type of the steroid drug administered. Moreover, further studies are needed to identify the optimal type and dosage.

High neutrophils and low lymphocytes percentages in bronchoalveolar lavage fluid are prognostic factors of higher in-hospital mortality in diffuse alveolar hemorrhage.

BACKGROUND: Diffuse alveolar hemorrhage (DAH) is a syndrome resulting from bleeding in the microcirculation of the lung, with a poor prognosis. The study aim was to identify prognostic factors of DAH, especially bronchoalveolar lavage fluids (BALF) cell pattern. METHODS: We conducted a single-center retrospective cohort study of patients diagnosed as having DAH and hospitalized at our hospital between October 2008 and July 2020. We performed univariate logistic regressions to identify variables associated with in-hospital death. RESULTS: Sixty-eight patients were included in our analysis. In-hospital mortality was 26.5%. Variables associated with in-hospital death were neutrophils percentage in BALF ≥ 44.5% [Odds Ratio (OR) 16.0, 95% confidence interval (CI) 4.33-58.9)], lymphocytes percentage in BALF < 14% (OR 7.44, 95% CI 2.11-26.2), idiopathic DAH (OR 0.31, 95% CI 0.10-0.95), oxygen flow ≥ 4L/min (OR 3.90, 95% CI 1.20-12.6), and estimated glomerular filtration rate < 60 mL/min (OR 5.00, 95%CI 1.29-19.4). CONCLUSIONS: High neutrophils and low lymphocytes percentages in BALF were associated with poor prognosis.

Pembrolizumab-Induced Meningoencephalitis: A Brain Autopsy Case.

Encephalitis is very rare, but often fatal immune-related adverse event (irAE) of immune checkpoint inhibitors (ICIs). A 65-year-old Japanese woman was admitted to our hospital because of general fatigue, chillness and high-grade fever for 4 days, 8 months after the initiation of the first-line pembrolizumab monotherapy for metastatic pulmonary adenocarcinoma. On the hospital day 3, she suddenly presented delirium and uncontrollable impaired consciousness. Although the magnetic resonance imaging (MRI) did not suggest a diagnosis of encephalitis and meningitis, the spinal fluid showed abnormally elevated levels of protein (317.6 mg/L) and cell count (197 cells/µL) with increased mononuclear cells (93%). An empirical and intravenous administration of acyclovir in doses of 10 mg/kg body weight every 8 h and steroid pulse therapy in dose of 1 g/body/day from the hospital day 5 until her death failed to improve her conditions. She died on the hospital day 8. The postmortem autopsy showed viable cancer cells in the metastatic tumor in the left occipital lobe and in the spinal fluids. However, many inflammatory cells infiltration in the meninges and perivascular cuffing were prominent especially in the brain stem and medial part of the temporal lobe. Infiltrating lymphocytes in the meninges and parenchyma of the brain stem were mainly composed of cluster of differentiation (CD)8-positive lymphocytes. For irAE encephalitis, early recognition of early signs and symptoms and subsequent early therapeutic intervention are necessary. It is important for oncologists to keep in mind of the possible adverse effects of immunotherapies on the nervous system.

Osimertinib-Induced Unilateral Diffuse Alveolar Hemorrhage in a Patient With Pulmonary Adenocarcinoma.

A 70-year-old man with lung adenocarcinoma was admitted to our hospital due to progressive dyspnea, 4 months after osimertinib initiation. His chest radiograph and computed tomography revealed ground-glass opacities and consolidations dominantly in the upper left lung. He took neither antiplatelet nor anticoagulation agent. No abnormality in coagulation was detected. Bronchoalveolar lavage fluid (BALF) became serially and increasingly hemorrhagic, and confirmed the diagnosis of alveolar hemorrhage. After steroid pulse therapy and withdrawal of osimertinib, his condition gradually improved, accompanied by regression of ground-glass opacities and consolidations. Osimertinib causes not only interstitial pneumonia but also alveolar hemorrhage. The consolidations may spread not bilaterally, but be localized unilaterally. We have to keep this rare adverse event in mind, and consider immediate withdrawal of osimertinib and treatment with steroid. Increased lymphocytes in the BALF may be a potential indicator of sensitivity to steroid and favorable prognosis in diffuse alveolar hemorrhage.

Transformation From Adenocarcinoma to Pleomorphic Carcinoma as an Acquired Resistance to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors.

Pulmonary pleomorphic carcinoma is a very rare histological type of primary lung cancer, and usually provides aggressive clinical courses. A 65-year-old Japanese woman was diagnosed by transbronchial biopsy of the primary tumor as c-stage IV (cT4N3M1b) of adenocarcinoma harboring L858R point mutation in the exon 21 of epidermal growth factor receptor (EGFR). She received EGFR tyrosine kinase inhibitors (TKIs) (gefitinib and erlotinib) and subsequently cytotoxic chemotherapies. Gefitinib achieved partial response, but was switched to erlotinib due to elevated serum aspartate transaminase. After resistance to EGFR-TKIs, the second transbronchial re-biopsy revealed pulmonary pleomorphic carcinoma. Both carcinomatous and sarcomatous components retained the L858R mutation, but did not acquire T790M mutation. This case suggested that the histological transformation to pulmonary pleomorphic carcinoma may be one of mechanisms of drug resistance to EGFR-TKIs.

Secondary organizing pneumonia after coronavirus disease 2019: Two cases.

Coronavirus disease 2019 (COVID-19) has been reported to induce persistent symptoms even after an acute phase. However, the pathophysiology and treatment of this condition have been unclear. We report two patients who recovered from COVID-19, but presented persistent respiratory symptoms. Their respiratory conditions deteriorated, and computed tomography showed remaining ground glass opacities and consolidations. The pathological findings of transbronchial lung biopsy corresponded to organizing pneumonia. We diagnosed them with secondary organizing pneumonia after COVID-19. Subsequently, we administered systemic corticosteroids. Their symptoms, oxygenations, radiologic findings, and pulmonary functions rapidly improved after the treatment of corticosteroids. The two cases showed that secondary organizing pneumonia may be a cause of persistent respiratory failure after COVID-19. In this condition, corticosteroids may be effective.

Osimertinib-induced cardiac failure with QT prolongation and torsade de pointes in a patient with advanced pulmonary adenocarcinoma.

Osimertinib-induced cardiotoxicity is a well-known but rare disorder. An 84-year-old woman was diagnosed with recurrence of lung adenocarcinoma showing an epidermal growth factor receptor mutation of exon 19 deletion, which was initially treated by curative-intent thoracic radiotherapy 4 years prior. She started taking osimertinib (80 mg/day). She had no history of heart disease and showed no signs of cardiac problems. However, 2 months later she presented with symptoms of cardiac failure and QT prolongation on electrocardiogram. Cardiac enzyme levels were not elevated and coronary computed tomography angiography showed no significant stenosis. On admission, sudden-onset torsade de pointes required electrocardioversion. Thus, drug-induced cardiac failure was strongly suspected and we stopped osimertinib therapy. Cardiac function and the electrocardiogram abnormality improved. To our knowledge, this is the third case of coincidence of cardiac failure and QT prolongation and the second case of sudden-onset torsade de pointes associated with osimertinib treatment. In our case, osimertinib-induced cardiac failure with QT prolongation was recovered by stopping the drug treatment. The potential for cardiotoxicity should be considered with osimertinib treatment.

Effectiveness of EGFR tyrosine kinase inhibitors in advanced non-small cell lung cancer patients with uncommon EGFR mutations: A multicenter observational study.

BACKGROUND: Epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) therapy is the standard treatment for advanced non-small cell lung cancer (NSCLC) harboring common EGFR mutations, such as exon 19 deletion or L858 point mutation. However, the effectiveness of EGFR-TKIs for patients with uncommon EGFR mutations remains unclear. METHODS: We retrospectively surveyed a consecutive database of NSCLC patients with EGFR mutations at five participating institutions. Data from NSCLC patients with uncommon mutations (including single or compound mutations), who were treated with systemic therapy between May 2016 and October 2018, were collected and analyzed. RESULTS: A total of 23 of the 524 patients whose data were collected had uncommon EGFR mutations. Of these, 22 received EGFR-TKIs (gefitinib = 6, erlotinib = 4, and afatinib = 12). Patients who received first EGFR-TKIs had overall response and disease control rates of 59.1% and 81.8%, respectively. The median progression-free survival (PFS) of patients with G719X mutation (n = 13, median PFS = 32.9 months) was favorable, compared with those of patients with L861Q mutation (n = 4, median PFS = 6.4 months) and compound mutations (n = 4, median PFS = 7.3 months). The PFS of patients who received first- and second-generation EGFR-TKIs was 14.0 months (n = 10) and 7.3 months (n = 12), respectively. The median cumulative duration of treatment (DOT) with EGFR-TKIs was 30.4 months, which was longer than those of cytotoxic chemotherapy (median DOT = 10.7 months) or immune checkpoint inhibitors (median DOT = 6.6 months). CONCLUSIONS: EGFR-TKIs elicit favorable responses and contribute to long-term disease control in NSCLC patients with uncommon EGFR mutations. KEY POINTS: Significant findings of the study: Our results demonstrate that both first- and second-generation EGFR-TKIs elicit favorable responses in NSCLC patients with uncommon EGFR mutations. What this study adds This study revealed all clinical courses for NSCLC patients with uncommon EGFR mutations. In addition to EGFR-TKIs, CCT and ICIs were found to contribute to long-term disease control in this cohort.

Sarcopenia and Visceral Adiposity Are Not Independent Prognostic Markers for Extensive Disease of Small-Cell Lung Cancer: A Single-Centered Retrospective Cohort Study.

BACKGROUND: Sarcopenia and visceral adiposity have been suggested to affect prognosis and treatment efficacy in various types of cancers. The aim of our study was to evaluate whether pretreatment sarcopenia and visceral adiposity are associated with prognosis in patients with extensive-disease small-cell lung cancer (ED-SCLC). METHODS: Between September 2007 and March 2018, 128 ED-SCLC patients received first-line and platinum-based chemotherapy at our hospital. Based on pretreatment body mass index (BMI), psoas muscle index (PMI), intramuscular adipose tissue content (IMAC) and visceral-to-subcutaneous fat ratio (VSR) at lumbar vertebra L3 level, we divided these patients into two groups, and then compared overall survival (OS) and progression-free survival (PFS). Adjusted by age, serum albumin, lactate dehydrogenase (LDH), clinical stage and performance status, we detected independent prognostic factors by multivariate Cox proportional hazard analyses. RESULTS: We did not find any significant differences in OS and PFS between two groups divided by BMI, PMI, IMAC and VSR. According to multivariate analyses, none of BMI, PMI, IMAC and VSR was an independent prognostic factor of OS and PFS. CONCLUSIONS: Neither pretreatment sarcopenia nor visceral adiposity is a prognostic marker of patients with ED-SCLC treated with standard regimen of platinum-based chemotherapy.

Successful Treatment of Allergic Bronchopulmonary Aspergillosis Using a Combination of Inhaled Fluticasone Furoate/Vilanterol and Oral Voriconazole.

Systemic corticosteroids are considered to be the standard treatment for allergic bronchopulmonary aspergillosis (ABPA). However, there is controversy regarding use of inhaled corticosteroid (ICS) therapy for ABPA. Here we report a case of ABPA that was successfully treated with inhaled fluticasone furoate/vilanterol (FF/VI) and oral voriconazole (VRCZ). The patient was a 62-year-old Japanese man with bronchiectasis and diabetes mellitus who presented with fever, cough, and purulent sputum. Computed tomography scans of the chest showed consolidation in the left upper and lower lobes. Laboratory investigations revealed an abnormal increase in the number of eosinophils (3,340/mm3) and elevated levels of C-reactive protein (3.04 mg/dL) and serum immunoglobulin E (IgE) (763 U/mL). Eight days after admission, he experienced a sudden attack of asthma. Aspergillus-precipitating antibodies were positive and Aspergillus fumigatus was detected in sputum culture. These results were consistent with a diagnosis of ABPA, and he was started on inhaled FF/VI and oral VRCZ. Systemic corticosteroids were not used because of the patient's history of diabetes mellitus and left atrial thrombus. His symptoms and consolidation improved significantly after treatment. He has not experienced an exacerbation for more than 3 years. In mild cases of ABPA in which total IgE is relatively low, inhaled FF/VI in combination with oral VRCZ can be considered as an alternative treatment to systemic corticosteroids in patients with ABPA.

Classification of idiopathic interstitial pneumonias using anti-myxovirus resistance-protein 1 autoantibody.

Chronic fibrosing idiopathic interstitial pneumonia (IIP) can be divided into two main types: idiopathic pulmonary fibrosis (IPF), a steroid-resistant and progressive disease with a median survival of 2-3 years, and idiopathic non-specific interstitial pneumonia (INSIP), a steroid-sensitive and non-progressive autoimmune disease. Although the clinical courses of these two diseases differ, they may be difficult to distinguish at diagnosis. We performed a comprehensive analysis of serum autoantibodies from patients definitively diagnosed with IPF, INSIP, autoimmune pulmonary alveolar proteinosis, and sarcoidosis. We identified disease-specific autoantibodies and enriched KEGG pathways unique to each disease, and demonstrated that IPF and INSIP are serologically distinct. Furthermore, we discovered a new INSIP-specific autoantibody, anti-myxovirus resistance-1 (MX1) autoantibody. Patients positive for anti-MX1 autoantibody constituted 17.5% of all cases of chronic fibrosing IIPs. Notably, patients rarely simultaneously carried the anti-MX1 autoantibody and the anti-aminoacyl-transfer RNA synthetase autoantibody, which is common in chronic fibrosing IIPs. Because MX1 is one of the most important interferon-inducible anti-viral genes, we have not only identified a new diagnostic autoantibody of INSIP but also obtained new insight into the pathology of INSIP, which may be associated with viral infection and autoimmunity.

Overcoming chemoresistance of small-cell lung cancer through stepwise HER2-targeted antibody-dependent cell-mediated cytotoxicity and VEGF-targeted antiangiogenesis.

Small-cell lung cancer (SCLC) easily recurs with a multidrug resistant phenotype. However, standard therapeutic strategies for relapsed SCLC remain unestablished. We found that human epidermal growth factor receptor 2 (HER2) is not only expressed in pretreated human SCLC specimens, but is also upregulated when HER2-positive SCLC cells acquire chemoresistance. Trastuzumab induced differential levels of antibody-dependent cell-mediated cytotoxicity (ADCC) to HER2-positive SCLC cells. Furthermore, as a mechanism of the differential levels of ADCC, we have revealed that coexpression of intracellular adhesion molecule (ICAM)-1 on SCLC cells is essential to facilitate and accelerate the trastuzumab-mediated ADCC. Although SN-38-resistant SCLC cells lacking ICAM-1 expression were still refractory to trastuzumab, their in vivo growth was significantly suppressed by bevacizumab treatment due to dependence on their distinctive and abundant production of vascular endothelial growth factor. Collectively, stepwise treatment with trastuzumab and bevacizumab is promising for the treatment of chemoresistant SCLC.

Involvement of STAT3 in immune evasion during lung tumorigenesis.

In a recent study, we have shown that STAT3 expressed by tumor cells blunts antitumor immunity during carcinogen-induced lung tumorigenesis. STAT3 inhibits the production of pro-inflammatory chemokines and MHC Class I chain-related gene A. In contrast, STAT3 promotes the expression of MHC class I molecules. Consequently, STAT3 promotes tumor cell resistance to NK cell-mediated cytotoxicity.

Inhibitory roles of signal transducer and activator of transcription 3 in antitumor immunity during carcinogen-induced lung tumorigenesis.

Stat3 mediates a complex spectrum of cellular responses, including inflammation, cell proliferation, and apoptosis. Although evidence exists in support of a positive role for Stat3 in cancer, its role has remained somewhat controversial because of insufficient study of how its genetic deletion may affect carcinogenesis in various tissues. In this study, we show using epithelium-specific knockout mice (Stat3(Δ/Δ)) that Stat3 blunts rather than supports antitumor immunity in carcinogen-induced lung tumorigenesis. Although Stat3(Δ/Δ) mice did not show any lung defects in terms of proliferation, apoptosis, or angiogenesis, they exhibited reduced urethane-induced tumorigenesis and increased antitumor inflammation and natural killer (NK) cell immunity. Comparative microarray analysis revealed an increase in Stat3(Δ/Δ) tumors in proinflammatory chemokine production and a decrease in MHC class I antigen expression associated with NK cell recognition. Consistent with these findings, human non-small cell lung cancer (NSCLC) cells in which Stat3 was silenced displayed an enhancement of proinflammatory chemokine production, reduced expression of MHC class I antigen, and increased susceptibility to NK cell-mediated cytotoxicity. In addition, supernatants from Stat3-silenced NSCLC cells promoted monocyte migration. Collectively, our findings argue that Stat3 exerts an inhibitory effect on antitumor NK cell immunity in the setting of carcinogen-induced tumorigenesis.

Tetraspanin CD151 protects against pulmonary fibrosis by maintaining epithelial integrity.

RATIONALE: Idiopathic pulmonary fibrosis (IPF) is a chronic pulmonary disorder of unknown etiology with few treatment options. Although tetraspanins are involved in various diseases, their roles in fibrosis have not been determined. OBJECTIVES: To investigate the role of tetraspanin CD151 in pulmonary fibrosis. METHODS: CD151 knockout (KO) mice were studied by histological, biochemical, and physiological analyses and compared with wild-type mice and CD9 KO mice. Further mechanistic analyses were performed in vitro, in vivo, and on samples from patients with IPF. MEASUREMENTS AND MAIN RESULTS: A microarray study identified an enrichment of genes involved in connective tissue disorders in the lungs of CD151 KO mice, but not in CD9 KO mice. Consistent with this, CD151 KO mice spontaneously exhibited age-related pulmonary fibrosis. Deletion of CD151 did not affect pulmonary fibroblast functions but instead degraded epithelial integrity via attenuated adhesion strength on the basement membrane; CD151-deleted alveolar epithelial cells exhibited increased α-SMA expression with activation of p-Smad2, leading to fibrotic changes in the lungs. This loss of epithelial integrity in CD151 KO lungs was further exacerbated by intratracheal bleomycin exposure, resulting in severe fibrosis with increased mortality. We also observed decreased numbers of CD151-positive alveolar epithelial cells in patients with IPF. CONCLUSIONS: CD151 is essential for normal function of alveolar epithelial cells; loss of CD151 causes pulmonary fibrosis as a result of epithelial disintegrity. Given that CD151 may protect against fibrosis, this protein represents a novel target for the treatment of fibrotic diseases.

Recurrent allergic bronchopulmonary aspergillosis in a patient with rheumatoid arthritis treated with etanercept and tocilizumab.

We report the case of a 68-year-old woman with Stage III and Class II rheumatoid arthritis (RA) that was resistant to prednisolone, methotrexate, and infliximab. After treatment with etanercept or tocilizumab, suspicious allergic bronchopulmonary aspergillosis (ABPA) repeatedly occurred and then rapidly improved after the withdrawal of each drug. We suspect that administration of etanercept and tocilizumab caused suspicious ABPA in this patient. The relevance to the pathogenesis of ABPA under these biological drugs is also discussed.