Clinical Characteristics of Relapsing Polychondritis: A Report of 8 Cases in Japan.

OBJECTIVES: Relapsing polychondritis (RP) is a very rare autoimmune disorder characterized by recurrent episodes of inflammation and destruction of cartilaginous tissues. We examined the clinical characteristics, management, and outcomes of Japanese RP patients. METHODS: We identified 8 RP cases in our department between 2003 and 2017. Detailed clinical features, testing, treatment, and outcomes were recorded. RESULTS: The mean time from symptom onset to diagnosis was 9 months. Four cases presented with auricular chondritis and laryngotracheal involvement and 3 cases presented with a saddle nose deformity. Anti-type II collagen antibody was positive in 5 of 6 cases. Of 3 cases with associated diseases (rheumatoid arthritis, ulcerative colitis, and Sjögren's syndrome), 2 died of respiratory failure. CONCLUSIONS: When RP is diagnosed, early computed tomography or pulmonary function testing is essential to enable early treatment. Undiagnosed airway involvement can cause tracheobronchial wall fibrosis, leading to fixed stenosis.

[Two cases of bronchial asthma diagnosed as hyperventilation syndrome].

We report two cases of bronchial asthma masked by hyperventilation syndrome. Case 1 was a 43-year-old woman. She had repeatedly visited the emergency room complaining of dyspnea and had been given a diagnosis of hyperventilation syndrome for 8 years. Initially, her symptom was only coughing, however, dyspnea gradually appeared. We suspected her symptoms were caused by bronchial asthma on the basis of her wheezes, and we established a diagnosis based on the results of the airway reversible test. Case 2 was a 24-year-old woman. She also had repeatedly visited the emergency room, supposedly because of hyperventilation syndrome over the long term. The airway reversible test revealed that she had features of asthma. After treatment for bronchial asthma, the asthma attacks subsided. After that, neither patient made any emergency visits. We should auscultate the respiratory sounds of patients with hyperventilation syndrome carefully. Additionally, we may as well apply the spirometries and the airway reversible test during a period of stability to a patient who has repeated hyperventilation attacks.

Association of anti-aminoacyl-transfer RNA synthetase antibody and anti-melanoma differentiation-associated gene 5 antibody with the therapeutic response of polymyositis/dermatomyositis-associated interstitial lung disease.

BACKGROUND: We attempted to clarify whether the presence of anti-aminoacyl-transfer RNA synthetase antibody (anti-ARS Ab) or anti-melanoma differentiation-associated gene 5 antibody (anti-MDA5 Ab) is associated with the therapeutic response of polymyositis/dermatomyositis-associated interstitial lung disease (PM/DM-ILD). METHODS: We retrospectively investigated 22 patients with PM/DM-ILD (10 positive for anti-ARS Ab and nine positive for anti-MDA5 Ab) for whom antibody analysis of conserved serum was possible. We assessed mortality in the first three months as the therapeutic response in the acute phase and compared changes in clinical data for up to one year considered as the chronic phase. We classified the clinical changes over the year into three groups: Improvement (increased % vital capacity [%VC] or diffusing capacity of the lung for carbon monoxide [%DLCO]≥10 or 15%), deterioration (decreased %VC or %DLCO≥10 or 15%), and no change (remainder of the changes). The extent of abnormality demonstrated by high-resolution computed tomography (HRCT) was scored. RESULTS: Positivity for anti-MDA5 Ab, but not for anti-ARS Ab, was associated with mortality in the first 3 months. Evaluation of the therapeutic response in the first year showed that positivity for the anti-ARS Ab, but not for the anti-MDA5 Ab, was associated with an improvement in %DLCO and a decline in the serum KL-6 levels. Positivity for the anti-ARS Ab or negativity for anti-MDA5 Ab was associated with a greater decrease in bronchial dilatation as seen by HRCT. CONCLUSIONS: Anti-ARS and anti-MDA5 Abs are associated with the therapeutic response of PM/DM-ILD.

A case of lipoid pneumonia caused by inhalation of vaporized paraffin from burning candles.

A 66-year-old woman was referred to our hospital for investigation of interstitial lung disease. She had spent most of her time in a shrine, and had always been exposed to vaporized paraffin from burning candles. Chest High-resolution computed tomography (HRCT)showed ground-glass attenuation with thickening of septal lines, wh create the so-called "crazy-paving appearance". Although bronchoalveolar lavage(BAL) and transbronchial biopsy were performed to aid in diagnosis, the findings did not reveal any conclusive information. Improvements on chest radiographs and in the patient's symptoms were observed without any therapeutic intervention; however, one year later, her chest X-ray showed deteriorative changes. Surgical lung biopsy was performed, and the pathological findings were consistent with those of lipoid pneumonia. The patient showed spontaneous remission of the disease. The cause of exogenous lipoid pneumonia was attributed to inhalation of vaporized paraffin from burning candles in the shrine. This is the first case of lipoid pneumonia that was found to develop from exposure to vaporized paraffin.

An Autopsy Case of Anti-melanoma Differentiation-associated Gene-5 Antibody-positive Clinical Amyopathic Dermatomyositis Complicated by Rapidly Progressive Interstitial Lung Disease.

A 62-year-old man presented with heliotrope rash, Gottron's sign, and mild muscle weakness. Both of his lung fields showed interstitial changes that worsened rapidly. He was diagnosed with clinical amyopathic dermatomyositis with rapidly progressive interstitial lung disease. The patient died of respiratory failure, despite the administration of immunosuppressive therapy. Autopsy revealed diffuse alveolar damage. An antibody analysis, which was performed postmortem, detected the presence of anti-melanoma differentiation-associated gene (MDA)-5 antibodies. Clinicians should note the clinical, radiologic, and serologic findings to predict anti-MDA-5 antibody-associated rapidly progressive interstitial lung disease.

[A case of Kimura's disease accompanied with bilateral, mediastinal and hilar lymphadenopathy].

A 52-year-old man presented with general fatigue and body weight loss. Chest X-ray and computed tomography showed bilateral, mediastinal and hilar lymphadenopathy. Laboratory tests revealed that peripheral eosinophils (1,850/microL) and serum IgE levels (1,610 U/L) were markedly increased. Cervical lymph node biopsy was performed for a definitive diagnosis. Histopathological analysis, using conventional H&E staining, showed mild infiltration of eosinophils into lymphoid follicules in the cervical lymph node. Immunohistopathological analysis, using an anti-human IgE antibody, showed mesh-like IgE positive staining in lymphoid follicles. These clinical and pathological findings are compatible with a diagnosis of Kimura's disease.

Serum level of periostin can predict long-term outcome of idiopathic pulmonary fibrosis.

BACKGROUND: KL-6 and surfactant proteins A and D are the only established serum biomarkers of idiopathic pulmonary fibrosis (IPF). We have previously shown that serum levels of periostin, a unique matricellular protein, are elevated and correlated with pulmonary function in patients with IPF. We sought to determine whether the serum periostin levels correlate with overall survival (OS) and time-to-event (TTE), as a parameter reflecting long-term outcome, and with the extent of abnormality on chest high-resolution computed tomography (HRCT) scores in patients with IPF. METHODS: Twenty-nine patients with IPF were analyzed retrospectively. The mean observation period was 1035.2 ± 663.1 days (range, 112-1800 days). High-resolution computed tomography (HRCT) scores were calculated based on the extent of abnormality evidenced by HRCT. We evaluated if there were any correlations between the serum periostin levels and clinical parameters, including HRCT score, using Spearman's rank correlation coefficients and analyzed predictors of OS and TTE using the log-rank tests. RESULTS: We showed that the serum periostin levels significantly correlated with the increase of honeycombing score on HRCT during a 6-month period. Log-rank tests showed that a higher serum periostin level was a predictor of a shortened OS and TTE. Greater extents of fibrotic lesions on HRCT scan were predictors of shortened OS and TTE. CONCLUSIONS: In IPF patients, the serum periostin level may be a good predictive biomarker for an increase in the radiological fibrotic area and long-term outcome.

[A case of hypersensitivity pneumonitis showing acute respiratory distress syndrome due to exposure to dust containing diphenylmethane diisocyanate].

The patient was a 61-year-old man who reported coughing and fever that occurred immediately after the work of breaking up a large refrigerator containing diphenylmethane diisocyanate (MDI). He was brought to our medical center with respiratory distress ten days after onset. Acute respiratory distress syndrome was diagnosed on the basis of a P/F oxygen ratio of less than 200 and chest CT findings of extended consolidation in both lung fields. He was intubated and ventilated mechanically. Steroid pulse therapy was started because of an elevated lymphocyte count found through bronchoalveolar lavage (BAL). After that, arterial blood gas and chest radiography findings improved gradually, and high-resolution chest findings on the 4th day of hospitalization showed centrilobular and uncleared shadows of marginated acini in both lung fields. The patient was extubated ten days after admission, the steroid therapy was withdrawn, and he was discharged from the intensive care unit on the 22nd day of hospitalization. Transbronchial lung biopsy on admission revealed alveolitis, Masson bodies and activated macrophages in the air spaces. The dismantled refrigerator was known to contain MDI, and because of the IgE and the IgG to MDI present in the serum, and of the IgG to MDI in the BAL fluid, we diagnosed hypersensitivity pneumonitis with acute respiratory distress syndrome due to exposure to dust containing MDI. There are many reports of painters with hypersensitivity pneumonitis following exposure to isocyanates, but care should be taken to avoid the possibility of acute respiratory distress syndrome arising because of the inhalation of dust mixed with isocyanates.

Interstitial Pneumonia associated with ulcerative colitis: high-resolution computed tomography and pathologic findings.

Pulmonary parenchymal manifestations associated with ulcerative colitis (UC) include various conditions such as opportunistic infections, interstitial pneumonia, organizing pneumonia, and adverse drug reactions. We present a case of interstitial pneumonia associated with UC in a 61-year-old nonsmoking woman. High-resolution computed tomography demonstrated multifocal ill-defined areas of consolidation and ground-glass attenuation with or without traction bronchiectasis, predominantly in peripheral lung parenchyma. Lung biopsy showed that the closest pathologic pattern in the areas of abnormality was cellular and fibrotic nonspecific interstitial pneumonia. We also discuss the evaluation and treatment of pulmonary disease possibly related to UC in the clinical course of this patient.

IL-18 induces airway hyperresponsiveness and pulmonary inflammation via CD4+ T cell and IL-13.

IL-18 plays a key role in the pathogenesis of pulmonary inflammatory diseases including pulmonary infection, pulmonary fibrosis, lung injury and chronic obstructive pulmonary disease (COPD). However, it is unknown whether IL-18 plays any role in the pathogenesis of asthma. We hypothesized that overexpression of mature IL-18 protein in the lungs may exacerbate disease activities of asthma. We established lung-specific IL-18 transgenic mice on a Balb/c genetic background. Female mice sensitized- and challenged- with antigen (ovalbumin) were used as a mouse asthma model. Pulmonary inflammation and emphysema were not observed in the lungs of naïve transgenic mice. However, airway hyperresponsiveness and airway inflammatory cells accompanied with CD4(+) T cells, CD8(+) T cells, eosinophils, neutrophils, and macrophages were significantly increased in ovalbumin-sensitized and challenged transgenic mice, as compared to wild type Balb/c mice. We also demonstrate that IL-18 induces IFN-γ, IL-13, and eotaxin in the lungs of ovalbumin-sensitized and challenged transgenic mice along with an increase in IL-13 producing CD4(+) T cells. Treatment with anti-CD4 monoclonal antibody or deletion of the IL-13 gene improves ovalbumin-induced airway hyperresponsiveness and reduces airway inflammatory cells in transgenic mice. Overexpressing the IL-18 protein in the lungs induces type 1 and type 2 cytokines and airway inflammation, and results in increasing airway hyperresponsiveness via CD4(+) T cells and IL-13 in asthma.

Chemotherapy for non-small cell lung cancer complicated by idiopathic interstitial pneumonia.

Idiopathic interstitial pneumonia (IIP) is considered to be one of the risk factors for lung cancer (LC). However, therapeutic options for patients with LC complicated by IIP are not well established. In this study, we investigated the feasibility and efficacy of chemotherapy for patients with non-small cell lung cancer (NSCLC) complicated by IIP (NSCLC-IIP). We retrospectively analyzed 22 NSCLC-IIP patients who received chemotherapy. To determine how IIP affected the clinical outcomes in NSCLC, they were compared with 276 NSCLC patients without IIP, who were treated with chemotherapy alone. The response rate (partial response + stable disease) was 72.3% (17/22), whereas the incidence of acute exacerbation (AE) was 13.6% (3/22) in NSCLC-IIP patients treated with chemotherapy. NSCLC-IIP patients had significantly shorter survival compared with NSCLC patients without IIP (P<0.001) following chemotherapy, although the response rates to chemotherapy were not significantly different between the two groups. Multivariate analysis demonstrated that, in NSCLC patients receiving chemotherapy, IIP was a significantly unfavorable factor for progression-free and overall survival. Despite similar response rates to chemotherapy, NSCLC-IIP patients showed poorer prognosis than NSCLC patients without IIP, possibly due to the natural course of IIP. Chemotherapy may be a feasible option for NSCLC-IIP, if the risks of adverse effects are acceptable.

A necrotic lung ball caused by co-infection with Candida and Streptococcus pneumoniae.

INTRODUCTION: A necrotic lung ball is a rare radiological feature that is sometimes seen in cases of pulmonary aspergillosis. This paper reports a rare occurrence of a necrotic lung ball in a young male caused by Candida and Streptococcus pneumoniae. CASE REPORT: A 28-year-old male with pulmonary candidiasis was found to have a lung ball on computed tomography (CT) of the chest. The patient was treated with ß-lactams and itraconazole and then fluconazole, which improved his condition (as found on a following chest CT scan) and serum ß-D-glucan level. The necrotic lung ball was suspected to have been caused by coinfection with Candida and S. pneumoniae. CONCLUSION: A necrotic lung ball can result from infection by Candida and/or S. pneumoniae, indicating that physicians should be aware that patients may still have a fungal infection of the lungs that could result in a lung ball, even when they do not have either Aspergillus antibodies or antigens.

Elevated levels of thioredoxin 1 in the lungs and sera of idiopathic pulmonary fibrosis, non-specific interstitial pneumonia and cryptogenic organizing pneumonia.

OBJECTIVE: Oxidant stress is thought to be involved in the establishment of idiopathic interstitial pneumonia (IIP). Thioredoxin 1 (TRX1) plays a role as a strong antioxidant in vivo, suggesting that TRX1 may be involved in the pathogenesis of IIPs. However, there is no report on TRX1 levels in the sera of IIPs. In addition, TRX1 expression in the lungs of non-specific interstitial pneumonia (NSIP) and cryptogenic organizing pneumonia (COP) patients also has not been reported. Here, we investigated whether or not TRX1 levels are altered in the lungs and sera of patients with idiopathic pulmonary fibrosis (IPF), NSIP, and COP. METHODS: Immunohistochemical analysis was performed to examine the expression of TRX1. TRX1 levels in sera were measured using an ELISA kit. RESULTS: TRX1 was expressed in the bronchiole-alveolar epithelium, especially with regenerative or metaplastic feature, and in alveolar macrophages in usual interstitial pneumonia (UIP) and fibrotic NSIP. TRX1 was weakly expressed in the lungs of cellular NSIP and COP. TRX1 producing cells in UIP (n=16), fibrotic NSIP (n=15), cellular NSIP (n=4), and COP (n=5) were significantly increased when compared to nonsmokers (n=7). TRX1 producing cells in UIP and fibrotic NSIP were significantly increased when compared to cellular NSIP and COP. TRX1 levels in the sera of the patients with IPF (n=32; 74.2 ± 7.5 ng/mL), fibrotic NSIP (n=7; 82.5 ± 18.4 ng/mL), cellular NSIP (n=3; 62.2 ± 3.2 ng/mL) and COP (n=17; 88.8 ± 19.7 ng/mL) were significantly higher than those of control subjects (n=74; 35.3 ± 2.7 ng/mL). Furthermore, TRX1 levels in the sera of IPF patients who later showed acute exacerbation (n=7; 106.6 ± 16.3 ng/mL) were significantly higher than those of IPF patients without acute exacerbation (n=25; 65.1 ± 7.6 ng/mL). CONCLUSION: Overproduction of TRX1 in the lungs and sera may play an important role in the pathogenesis of IIPs.