IgG4-related disease with tracheobronchial miliary nodules and asthma: a case report and review of the literature.
TL;DR: This case reported the first case of IgG4-RD presenting with miliary nodules on the tracheal and bronchial tube walls combined with asthma, and exhibited three important clinical indication: first, tracheobronchial miliary nodsules could be the presentation of Igg4-related disease, second, IgG 4- related disease with pulmonary involvement has close connection with asthma.
Abstract: IgG4-related disease (IgG4-RD) is a systemic autoimmune disease that can affect multiple organs of the body. Pulmonary manifestations of IgG4-RD include pulmonary solid nodules, thickening of bronchovascular bundles, interstitial involvement, and ground glass opacities. Here we present a rare case of IgG4-RD with tracheobronchial nodules and review the relevant literature. A 52-year-old man was admitted to our hospital with a history of intermittent cough for 27 months and recurrent wheezing for 17 months. He had been diagnosed with asthma prior to admission and was responsive to oral prednisone (30 mg/day, with gradual tapering). Bronchoscopy performed 2 years prior to admission showed tracheal and bronchial mucosal hyperemia, edema, and miliary nodules. Pathological tests showed chronic inflammation with focal lymphocytic infiltration in the bronchial mucosa. The patient had recurrent cough and wheezing after prednisone was stopped or the dose reduced. At the time of admission to our hospital, his serum immunoglobulin G4 (IgG4) level had increased to 7.35 g/L. Following bronchoscopy, the IgG4 expression in the bronchial mucosa was compared with that observed during the last two bronchoscopies. Bronchoscopy performed 7 months prior to admission revealed IgG4+ plasma cell infiltration in the bronchial tissue, with > 10 IgG4+ plasma cells per high power field and an IgG4+/IgG+ cell ratio of > 40%. The current bronchoscopy revealed a decrease in IgG4 expression in the bronchial tissue, probably because of the intermittent prednisone treatment. The case fulfilled the comprehensive clinical diagnostic criteria for IgG4-RD. He received prednisone and azathioprine, and he has never developed recurrence. Our case exhibited three important clinical indication: First, tracheobronchial miliary nodules could be the presentation of IgG4-related disease. Second, IgG4-related disease with pulmonary involvement has close connection with asthma. Last, IgG4-related disease can be very sensitive to prednisone, the infiltration of IgG4 positive plasma cells decreased after prednisone treatment and symptoms significantly improved in our case. In conclusion, we reported the first case of IgG4-RD presenting with miliary nodules on the tracheal and bronchial tube walls combined with asthma. The findings will further our understanding of the characteristics of IgG4-RD.
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TL;DR: A 53-year-old non-smoking Japanese woman was admitted to our hospital with a 20-year history of wet cough and dyspnoea on exertion, and her bronchial asthma had been diagnosed 20 years earlier as discussed by the authors.
Abstract: A 53-year-old non-smoking Japanese woman was admitted to our hospital with a 20-year history of wet cough and dyspnoea on exertion. Bronchial asthma (BA) had been diagnosed 20 years earlier. Although she has been treated with high-dose inhaled corticosteroid, she had experienced frequent exacerbation of BA, and short-term oral corticosteroid bursts were occasionally administered. High-resolution CT of the chest revealed diffuse centrilobular nodules with bronchial wall thickening and patchy ground-glass opacities in both lungs. Lung biopsy specimens showed widespread cellular bronchiolitis with follicle formations in the membranous and respiratory bronchioles, accompanied by marked infiltration of plasma cells and eosinophils. In addition, immunohistochemical immunoglobulin G4 (IgG4) staining revealed many IgG4-positive plasma cells, and the ratio of IgG4-positive cells to IgG-positive cells exceeded 40%. The final diagnosis was eosinophilic bronchiolitis with marked IgG4-positive plasma cell infiltration in association with BA. With benralizumab therapy, her clinical condition dramatically improved.
3 citations
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TL;DR: In this article , a 65-year-old Chinese male with an eight-year history of Kimura disease was admitted to the hospital with complaints of dyspnea and expectoration for one month.
Abstract: Immunoglobulin G4 (IgG4)-related disease (IgG4-RD) is a systemic disease that involves the infiltration of IgG4-positive plasma cells in multiple organs. Kimura disease (KD) presents as subcutaneous masses on the head and neck, frequently accompanied by eosinophilia and high immunoglobulin E (IgE) levels. Here, we report a rare case of concurrence of IgG4-RD and KD with manifestations of asthma, pulmonary embolism, and central diabetes insipidus accompanied by lung carcinoma.A 65-year-old Chinese male with an eight-year history of KD was admitted to our hospital with complaints of dyspnea and expectoration for one month. Laboratory examination showed a considerable elevation in the serum eosinophil count and total IgE and IgG4 levels. Chest enhanced computed tomography showed filling defects in the right pulmonary artery and a nodule in the left inferior lobe. Pancreatic enhanced magnetic resonance imaging (MRI) and magnetic resonance cholangiopancreatography showed a swollen pancreatic tail and local stricture of the pancreatic duct section of the common bile duct. Enhanced MRI of the pituitary gland showed thickening of the pituitary stalk. Additionally, immunohistochemistry of the specimens collected eight years prior revealed IgG4-positive cells. Following the diagnosis of IgG4-RD with KD, glucocorticoids with immunosuppressants were initiated; there was a prompt improvement in the patient's condition. One-year post-discharge, the patient underwent wedge-shaped resection of the lung due to enlargement of the pulmonary nodule, and the pathology revealed lung squamous carcinoma.This case presents a rare clinical condition in which the concurrence of IgG4-RD and KD causes various rare manifestations including asthma, pulmonary embolism, central diabetes insipidus, and complicated lung carcinoma. This highlights the importance of monitoring for malignancies in IgG4-RD patients during follow-up.
2 citations
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TL;DR: Wang et al. as discussed by the authors explored the clinical characteristics and prognoses of patients with immunoglobulin G4-related disease (IgG4-RD) manifesting as severe asthma.
Abstract: Respiratory involvement is common in immunoglobulin G4-related disease (IgG4-RD). However, severe asthma as the initial clinical manifestation of IgG4-RD is rare and might be neglected by respiratory clinicians. We aimed to explore the clinical characteristics and prognoses of patients with immunoglobulin G4-related disease (IgG4-RD) manifesting as severe asthma.A retrospective analysis of the clinical characteristics and prognoses of patients with severe asthma who were eventually diagnosed with IgG4-RD was performed in the Peking Union Medical College Hospital from 2013 to 2019.Twelve patients (5males, 7 females) were included. The mean age at enrollment and age of asthma onset were 59.4 ± 10.1 and 53.8 ± 10.4 years, respectively. The mean duration of asthma symptoms was 5.7 ± 2.0 years. In all patients, the proportion (25.1 ± 10.3%) and count (2.0 ± 1.1) × 109/L of eosinophils in peripheral blood increased. Additionally, all patients exhibited elevated total immunoglobulin E [IgE, (1279.3 ± 1257.9) KU/L] and IgG4 (9155.8 ± 9247.6) mg/dL. Bronchial wall thickening (n = 11) and mediastinal/hilar lymphadenopathy (n = 11) were major chest CT manifestations. All were pathologically diagnosed through surgical biopsy; submandibular gland (n = 8), supraclavicular lymph node (n = 2), stomach (n = 1), rashes (n = 1), lacrimal gland (n = 1) and thoracoscopic lung (n = 1) biopsies were performed. Asthma was well controlled by oral glucocorticoids (GCs), but some patients relapsed during tapering (n = 11). The refractory condition was controlled after increasing the dosage of GCs and add-on immunosuppressants.For patients with middle age-onset severe asthma with elevated eosinophils, total IgE and IgG4 levels and available salivary gland ultrasound imaging, ruling out IgG4-RD is recommended. GCs used in combination with immunosuppressants is recommended to prevent relapse.
2 citations
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TL;DR: The possible uncommon causes of chronic cough associated with airway eosinophilia, management of these uncommon causes, mechanistic insights linking eosInophilic airway inflammation and cough and management of eos inophilic infiltrates in the airways are described are described.
Abstract: J Thorac Dis 2021;13(5):3191-3196 | http://dx.doi.org/10.21037/jtd-20-2324 Chronic cough is defined as the sole or predominant symptom and lasting for more than 8 weeks, with a normal chest X-ray (1). The four common causes of chronic cough are cough-variant asthma (CVA), non-asthmatic eosinophilic bronchitis (NAEB), upper airway cough syndrome (UACS) and gastroesophageal reflux disease (GERD) (2). Eosinophilic airway inflammation, which is observed in 30% to 50% of chronic cough patients, is a common feature of CVA, NAEB and UACS. The response to corticosteroid therapy in these patients is generally very good (3). CVA, an airway disorder characterized by type 2-driven inflammation, is considered the most common cause of chronic cough (4). NAEB, another common cause of chronic cough, is characterized by airway eosinophilic inflammation without airway hyperresponsiveness (5). Previous studies F (6,7) have shown that the Th2 pathway also plays a role in NAEB. However, eosinophilic infiltrates in the airways, blood eosinophilia and chronic cough may be the main characteristics of other conditions, that do not respond to corticosteroid therapy. Type 2-driven inflammation does not appear to be the main mechanistic pathway underlying eosinophilic airway inflammation. Making a clear diagnosis, controll ing eosinophilic airway inflammation and managing cough can be difficult. In this editorial commentary, we describe (I) the possible uncommon causes of chronic cough associated with airway eosinophilia, (II) management of these uncommon causes of chronic cough and (III) mechanistic insights linking eosinophilic airway inflammation and cough. These uncommon conditions include (i) hypereosinophilic syndrome (HES), (ii) IgG4-related disease (IgG4-RD), (iii) Occupational eosinophilic bronchitis.
1 citations
Cites background from "IgG4-related disease with tracheobr..."
...It is commonly known that asthma often coincides with IgG4-RD (18-20)....
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...Nine case reports (18-20,23-28) showed that 11 patients (7 males and 4 females) with IgG4-RD had prolonged cough, with seven of them showing cough for over 1 year (18-20,23,24,27,28)....
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...Eosinophils were reported in 7 cases (18,19,23,25-28)....
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Adeel Nasrullah1, Anam Javed1, Zara Alvi1, Atif Raja1, Obaid Ashraf1, Khalid Malik1, Marvin Balaan1 •
TL;DR: In this article, the authors reviewed the 16 patients diagnosed with IgG4-related lung disease from October 2014 through December 2019 at their institution and found that three cases that showed pulmonary involvement were included in this series.
Abstract: IgG4-related lung disease is an extremely rare and novel entity which is still poorly understood. We reviewed the 16 patients diagnosed with IgG4-related disease from October 2014 through December 2019 at our institution. The three cases that showed pulmonary involvement are included in this series. Of these, two patients had cavitary lung disease and developed aspergilloma and chronic cavitating aspergillosis after a prolonged course of steroid therapy, and one had isolated pulmonary nodule and ground glass opacity. We reviewed the updated literature and briefly described disease epidemiology, clinical characteristics, diagnostic approaches, and management strategies for IgG4-related lung disease.
1 citations
References
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TL;DR: Patients with sclerosing pancreatitis have high serum IgG4 concentrations, providing a useful means of distinguishing this disorder from other diseases of the pancreas or biliary tract.
Abstract: Background Sclerosing pancreatitis is a unique form of pancreatitis that is characterized by irregular narrowing of the main pancreatic duct, lymphoplasmacytic inflammation of the pancreas, and hypergammaglobulinemia and that responds to glucocorticoid treatment. Preliminary studies suggested that serum IgG4 concentrations are elevated in this disease but not in other diseases of the pancreas or biliary tract. Methods We measured serum IgG4 concentrations using single radial immunodiffusion and an enzyme-linked immunosorbent assay in 20 patients with sclerosing pancreatitis, 20 age- and sex-matched normal subjects, and 154 patients with pancreatic cancer, ordinary chronic pancreatitis, primary biliary cirrhosis, primary sclerosing cholangitis, or Sjogren's syndrome. Serum concentrations of immune complexes and the IgG4 subclass of immune complexes were determined by means of an enzyme-linked immunosorbent assay with monoclonal rheumatoid factor. Results The median serum IgG4 concentration in the patients ...
2,355 citations
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Vikram Deshpande1, Yoh Zen2, John Kc Chan, Eunhee E Yi3, Yasuharu Sato4, Tadashi Yoshino4, Günter Klöppel5, J. Godfrey Heathcote6, Arezou Khosroshahi1, Judith A. Ferry1, Rob C. Aalberse7, Daniel Bloch1, William R. Brugge1, Adrian C Bateman8, Mollie N. Carruthers1, Suresh T. Chari3, Wah Cheuk, Lynn D. Cornell3, Carlos Fernandez-del Castillo1, David G. Forcione1, Daniel L. Hamilos1, Terumi Kamisawa9, Satomi Kasashima, Shigeyuki Kawa10, Mitsuhiro Kawano11, Gregory Y. Lauwers1, Yasufumi Masaki12, Yasuni Nakanuma11, Kenji Notohara, Kazuichi Okazaki13, Ji Kon Ryu14, Takako Saeki, Dushyant V. Sahani1, Thomas C. Smyrk3, James Robert Stone1, Masayuki Takahira11, George Webster15, Motohisa Yamamoto16, Giuseppe Zamboni17, Hisanori Umehara12, John H. Stone1 •
Harvard University1, University of Cambridge2, Mayo Clinic3, Okayama University4, Technische Universität München5, Dalhousie University6, University of Amsterdam7, Southampton General Hospital8, Tokyo Metropolitan Komagome Hospital9, Shinshu University10, Kanazawa University11, Kanazawa Medical University12, Kansai Medical University13, Seoul National University14, University College London15, Sapporo Medical University16, University of Verona17
TL;DR: This statement proposes a terminology scheme for the diagnosis of IgG4-related disease that is based primarily on the morphological appearance on biopsy, and advocates the use of strict criteria for accepting newly proposed entities or sites as components of the IgG 4- related disease spectrum.
2,041 citations
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Hisanori Umehara1, Kazuichi Okazaki2, Yasufumi Masaki1, Mitsuhiro Kawano3, Motohisa Yamamoto4, Takako Saeki, Shoko Matsui5, Tadashi Yoshino6, Shigeo Nakamura7, Shigeyuki Kawa8, Hideaki Hamano8, Terumi Kamisawa9, Toru Shimosegawa10, Akira Shimatsu, Seiji Nakamura11, Tetsuhide Ito11, Kenji Notohara1, Takayuki Sumida12, Yoshiya Tanaka, Tsuneyo Mimori13, Tsutomu Chiba13, Michiaki Mishima13, Toshifumi Hibi14, Hirohito Tsubouchi15, Kazuo Inui16, Hirotaka Ohara17 •
Kanazawa Medical University1, Kansai Medical University2, Kanazawa University3, Sapporo Medical University4, University of Toyama5, Okayama University6, Nagoya University7, Shinshu University8, Tokyo Metropolitan Komagome Hospital9, Tohoku University10, Kyushu University11, University of Tsukuba12, Kyoto University13, Keio University14, Kagoshima University15, Fujita Health University16, Nagoya City University17
TL;DR: The comprehensive diagnostic criteria for IgG4-RD are practically useful for general physicians and nonspecialists and have increased the sensitivity of diagnosis to 100% for Igg4-related MD, KD, and AIP.
Abstract: IgG4-related disease (IgG4-RD) is a novel clinical disease entity characterized by elevated serum IgG4 concentration and tumefaction or tissue infiltration by IgG4+ plasma cells Although IgG4-RD is not rare and is clinically important, its clinical diagnostic criteria have not been established Comprehensive diagnostic criteria for IgG4-RD, including the involvement of various organs, are intended for the practical use of general physicians and nonspecialists Two IgG4-RD study groups, the Umehara and Okazaki teams, were organized by the Ministry of Health, Labor and Welfare Japan As IgG4-RD comprises a wide variety of diseases, these groups consist of physicians and researchers in various disciplines, including rheumatology, hematology, gastroenterology, nephrology, pulmonology, ophthalmology, odontology, pathology, statistics, and basic and molecular immunology throughout Japan, with 66 and 56 members of the Umehara and Okazaki teams, respectively Collaborations of the two study groups involved detailed analyses of clinical symptoms, laboratory results, and biopsy specimens of patients with IgG4-RD, resulting in the establishment of comprehensive diagnostic criteria for IgG4-RD Although many patients with IgG4-RD have lesions in several organs, either synchronously or metachronously, and the pathological features of each organ differ, consensus has been reached on two diagnostic criteria for IgG4RD: (1) serum IgG4 concentration >135 mg/dl, and (2) >40% of IgG+ plasma cells being IgG4+ and >10 cells/high powered field of biopsy sample Although the comprehensive diagnostic criteria are not sufficiently sensitive for the diagnosis of type 1 IgG4-related autoimmune pancreatitis (IgG4-related AIP), they are adequately sensitive for IgG4-related Mikulicz’s disease (MD) and kidney disease (KD) In addition, the comprehensive diagnostic criteria, combined with organ-specific diagnostic criteria, have increased the sensitivity of diagnosis to 100% for IgG4-related MD, KD, and AIP Our comprehensive diagnostic criteria for IgG4-RD are practically useful for general physicians and nonspecialists
1,417 citations
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TL;DR: IL-13 is another T-cell-derived cytokine that, in addition to IL-4, efficiently directs naive human B cells to switch to IgG4 and IgE production, suggesting that common signaling pathways may be involved.
Abstract: Recently the cDNA encoding interleukin 13 (IL-13), a T-cell-derived cytokine, was cloned and expressed. The present study demonstrates that IL-13 induces IgG4 and IgE synthesis by human B cells. IL-13-induced IgG4 and IgE synthesis by unfractionated peripheral blood mononuclear cells and highly purified B cells cultured in the presence of activated CD4+ T cells or their membranes. IL-13-induced IgG4 and IgE synthesis is IL-4-independent, since it was not affected by neutralizing anti-IL-4 monoclonal antibody. Highly purified, surface IgD+ B cells could also be induced to produce IgG4 and IgE by IL-13, indicating that the production of these isotypes reflected IgG4 and IgE switching and not a selective outgrowth of committed B cells. IL-4 and IL-13 added together at optimal concentrations had no additive or synergistic effect, suggesting that common signaling pathways may be involved. This notion is supported by the observation that IL-13, like IL-4, induced CD23 expression on B cells and enhanced CD72, surface IgM, and class II major histocompatibility complex antigen expression. In addition, like IL-4, IL-13 induced germ-line IgE heavy-chain gene transcription in highly purified B cells. Collectively, our data indicate that IL-13 is another T-cell-derived cytokine that, in addition to IL-4, efficiently directs naive human B cells to switch to IgG4 and IgE production.
1,005 citations
01 Jan 2016
TL;DR: In this article, the cDNA encoding interleukin 13 (IL-13), a T-cell-derived cytokine, was cloned and expressed, and it was shown that IL-13 induces IgG4 and IgE synthesis by human B cells.
Abstract: Recently the cDNA encoding interleukin 13 (IL-13), a T-cell-derived cytokine, was cloned and expressed. The present study demonstrates that IL-13 induces IgG4 and IgE synthesis by human B cells. IL-13-induced IgG4 and IgE synthesis by unfractionated peripheral blood mononuclear cells and highly purified B cells cultured in the presence of activated CD4+ T cells or their membranes. IL-13-induced IgG4 and IgE synthesis is IL-4-independent, since it was not affected by neutralizing anti-IL-4 monoclonal antibody. Highly purified, surface IgD+ B cells could also be induced to produce IgG4 and IgE by IL-13, indicating that the production of these isotypes reflected IgG4 and IgE switching and not a selective outgrowth of committed B cells. IL-4 and IL-13 added together at optimal concentrations had no additive or synergistic effect, suggesting that common signaling pathways may be involved. This notion is supported by the observation that IL-13, like IL-4, induced CD23 expression on B cells and enhanced CD72, surface IgM, and class II major histocompatibility complex antigen expression. In addition, like IL-4, IL-13 induced germ-line IgE heavy-chain gene transcription in highly purified B cells. Collectively, our data indicate that IL-13 is another T-cell-derived cytokine that, in addition to IL-4, efficiently directs naive human B cells to switch to IgG4 and IgE production.
1,004 citations
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