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.

https://casereports.bmj.com/content/bmjcr/14/10/e246058.full.pdf

Eosinophilic bronchiolitis successfully treated with benralizumab.

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. 

/pdf/concurrence-of-igg4-related-disease-and-kimura-disease-with-w7nc59dk.pdf

Concurrence of IgG4-related disease and Kimura disease with pulmonary embolism and lung cancer: a case report

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. 

/pdf/severe-asthma-as-the-initial-clinical-manifestation-of-igg4-1x9heiia.pdf

Severe asthma as the initial clinical manifestation of IgG4-related disease: a retrospective clinical study

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.

/pdf/uncommon-causes-of-chronic-cough-associated-with-airway-1qnz93ts0k.pdf

Uncommon causes of chronic cough associated with airway eosinophilia

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.

IgG4 related lung disease- a rare and novel mimic of malignancy and infections-a case series of three patients with a brief review of updated literature.

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.

/pdf/igg4-related-disease-with-tracheobronchial-miliary-nodules-3d1t1d1ufw.pdf

Zhenguo Zhai

Papers

IgG4-related disease with tracheobronchial miliary nodules and asthma: a case report and review of the literature.