Authors: Zhu Wenyan, Li Yuhong, Zhang Ting, Peng Min, Feng Rui'e, Shi Juhong
Affiliation: Department of Respiratory and Critical Care Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College; Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Qinghai University; Department of Respiratory and Critical Care Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College; Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
Cite this article: Zhu Wenyan, Li Yuhong, Zhang Ting, et al. Diffuse thickening of bronchial wall with multiple nodular bulges [J] . Chinese Journal of Tuberculosis and Respiration, 2024, 47(4) : 346-351. DOI: 10.3760/cma.j.cn112147-20230913-00156.
summary
In this paper, a 58-year-old female patient was presented with "nasal congestion, sore throat, cough for 6 months, and breath holding for 5 months". Dry mouth for 1 year in medical history. Physical examination reveals flaky tooth loss, parotid glands, submandibular glands, and cervical lymphadenopathy, and rales in the lungs. Parotography shows that the branch ducts are not visible, and the distal ducts are cloudy and have slow emptying. Pathological labial gland biopsy shows focal lymphatic infiltrates. Chest CT showed diffuse thickening of the trachea and bilateral bronchial tubes, and extensive nodules of the trachea and bilateral bronchial mucosa under tracheoscopy. Bronchoscopic biopsy shows peribronchial lymphocytic infiltrates. The patient was diagnosed with Sjögren's syndrome and treated with glucocorticoids. Prednisone starts at 30 mg/day and tapered gradually. After glucocorticoid therapy, the clinical symptoms were relieved, the enlargement of lymph nodes, bilateral submandibular glands and parotid glands subsided, the bronchial thickening showed improvement on CT, and the multiple nodular bulges of the mucosa submerged under tracheoscopy subsided, and the large airways of Sjögren's syndrome were finally diagnosed. In Sjögren's syndrome airway involvement, small airway involvement such as bronchiolitis and bronchiectasis is common, but large airway involvement, particularly multiple cases of multiple nodules in the airways, is rare. In this case, the diagnosis was confirmed by clinical features, imaging, bronchoscopy, and pathological features, combined with treatment response.
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The patient, a 58-year-old woman, was admitted to the hospital on 13 May 2014 with "nasal congestion, sore throat, cough for 6 months, and breath holding for 5 months". At the beginning of November 2013, the patient developed fever after a cold, with a peak body temperature of 38.0 °C, accompanied by bilateral nasal congestion, sore throat, cough, and white sticky sputum. Presented to the local hospital, sinus CT: bilateral maxillary sinus, ethmoid sinus and sphenoid sinusitis, bilateral turbinate enlargement; laryngoscopy: bilateral inferior turbinate hypertrophy, lymphofollicular hyperplasia visible in the posterior pharyngeal wall; After receiving cefoperazone sulbactam infusion, the patient developed inner ear itching, buccal mucosa and tongue mucosa bulge with obvious pain the next day. Since December 2013, the patient has recurrent fever, cough and sputum production, and gradually develops breath-holding, bilateral submandibular glands, parotid glands and cervical lymph nodes are swollen and tender. Follow-up laryngoscopy in January 2014: irregular mucosal protrusions were seen in the subglottic and airway walls. CT chest (Figs. 1, 2): main bronchial mucosal hypertrophy and lumen stenosis. bronchoscopy: swelling of the glottis mucosa; multiple nodular bulges in the trachea, swelling of the mucous membranes; The carina widens, the left and right main bronchial mucosa is diffuse nodular bulge, and the lumen is narrow. mucosal biopsy shows acute and chronic inflammation with lymphocytic, plasmacytic, neutrophil, and eosinophil infiltrates; Special staining Congo red (-), PAS staining (-) and hexamine silver staining (-). Labial gland biopsy shows lymphocytic infiltrate in small salivary gland tissue. The local hospital treated the infection, and the patient's body temperature dropped to normal, but the submandibular gland, parotid gland and neck lymphadenopathy, sore throat, and breathlessness did not improve. With the addition of methylprednisolone (specific dosage and course of treatment unknown), the parotid gland, submandibular gland and cervical lymphadenopathy were better than before. He was admitted to the department for further diagnosis and treatment. In the past 1 year, the patient has had dry mouth, steamed buns and water to eat, teeth flaky loss, no dry eyes, denial of Raynaud's phenomenon, joint swelling and pain, rash, hearing loss, vision loss or change in the shape of the pinna.
Figs. 1,2 Multiple small nodules in both lungs on chest CT (January 2014) and bilateral main bronchial wall thickening in the mediastinal window: lacunar cerebral infarction was diagnosed in 2013 and diabetes mellitus was diagnosed in 2014. There is no special personal history, marital history, or family history. Physical examination: body temperature 36.5 °C, pulse rate 90 beats/min, respiratory rate 20 breaths/minute, blood pressure 118/77 mmHg (1 mmHg = 0.133 kPa), SpO2 94% (inhaled air). There is no enlargement of the parotid glands on both sides. Lymph nodes of 0.5~2 cm can be palpated in front of both ears, under the mandibular and behind the left neck, with clear borders, fixed positions and no tenderness. There is no deformity of the auricle. The lips are ruddy, the pharynx is not congested, the mouth is full of dentures, the right tongue margin is chapped, the buccal mucosa is rough, the tonsils are not significantly enlarged, and the jugular veins are not filled. Inspiratory and expiratory sputum sounds can be heard in both lungs and disappear when sitting. Laboratory tests: blood leukocytes 9.26×109/L [normal reference value: (3.50~9.50)×109/L], neutrophil count 6.51×109/L [normal reference value: (2.00~7.50)×109/L], eosinophil percentage 8.1% (normal reference value: 0.5%~5.0%), eosinophil count 0.75×109/L [normal reference value: (0.02~0.50)×109/L], Hemoglobin 127 g/L (normal reference value: 120~160 g/L), platelets 385×109/L [normal reference value: (100~350) ×109/L]. The blood smear showed no obvious abnormalities. ESR was 40 mm/1 h (normal reference value: 10~20 mm/1 h); Hypersensitive C-reactive protein 21.35 mg/L (normal reference value: 0~3.00 mg/L), angiotensin-converting enzyme 58 U/L (normal reference value: 12.0~68.0 U/L); sputum and alveolar lavage fluid pathogens (bacterial, fungal, tuberculous/nontuberculous mycobacteria) were negative; Three immunoglobulins, hematuria immunofixation electrophoresis, complement C3, C4 (-), antinuclear antibody, SSA, SSB, antineutrophil cytoplasmic antibody, IgG subclass (-). Ultrasound of bilateral neck and supraclavicular lymph nodes shows multiple hypoechoic lymph nodes under the mandibular without abnormal blood flow. There was no significant change in chest CT in June 2014 compared with January 2014. Pulmonary function tests showed that FEV1 accounted for 66.4% of the predicted value, FEV1/FVC was 66.88%, FVC was 82.7% of the predicted value, and DLCO was 86.9% of the predicted value. The saliva flow rate was 0.04 ml/min (normal reference value: >0.05 ml/min). Parotid glandography shows normal lead ducts, branch ducts are not visible, and the distal ducts are cloudy and slow to empty. Laryngoscopy reveals multiple irregular mucosal prominences in the left posterior nostril and posterior nasopharyngeal parietal wall, bilateral interphisal mucosal surfaces, and subglottic airway mucosal surfaces. Bronchoscopy (Fig. 3~10): tracheal cartilage ring is present, the mucosa is widely noduled, brittle, easy to bleed to the touch, and the bilateral bronchial mucosa is widely noduled, and the mucosa is congested. Bronchial mucosal pathology (Fig. 11) showed acute and chronic inflammation with more local eosinophilic infiltration; The airway mucosal epithelium is intact and there is no lymphatic follicular hyperplasia. Professor Liu Hongrui consulted on the pathology of lip gland biopsy in the hospital, and focal lymphocytic infiltration was seen around the labial gland.
Fig.3~10 Bronchoscopy (May 2014) showed small mucosal nodules of the positive airway and bronchial extensiveness at all levels
Fig.11 Bronchial mucosal biopsy (May 2014) showed acute and chronic inflammation of the bronchial mucosa, intact airway mucosal epithelium, and no lymphatic follicular hyperplasia with moderate magnification of HE
Figs. 12,13 Chest CT examination after regular hormonal therapy (August 2018) showed that the walls of the bilateral main bronchial tubes were generally normal
Diagnosis: Sjögren's syndrome; The nature of the lesion in the large airways is to be determined
In June 2014, the patient was treated with prednisone 30 mg/d, and the patient's symptoms such as dry mouth, cough and sputum, and breathlessness gradually improved. In February 2015, chest CT showed improvement in bronchial wall thickening, and multiple nodules on bronchoscopy significantly resolved compared with before. In October 2016, pulmonary function showed that FEV1 accounted for 109.4% of the predicted value, FEV1/FVC was 83.23%, and FVC accounted for 109.5% of the predicted value. In August 2018, chest CT showed that the bronchial wall was generally normal (Figs. 12, 13), and bronchoscopy (Figs. 14~21) showed that only mucosal nodules were scattered at the opening of the basal segment of the left lower lobe.
Fig.14~21 Bronchoscopy (August 2018) showed that the left lower lobe basal segment opening mucosal nodules were finally diagnosed with Sjögren's syndrome due to the patient's good response to glucocorticoids. Follow-up to October 2019, the patient had no discomfort such as dry mouth, cough and sputum, and breath-holding.
discuss
Ting Zhang (Department of Respiratory and Critical Care Medicine): Characteristics of this case: (1) middle-aged female, chronic course; (2) The clinical manifestations are dry mouth, flaky tooth loss, nasal congestion, cough and sputum, and breath-holding; In the course of the disease, there are manifestations of otolaryngal involvement and enlargement of submandibular and parotid glands; (3) Physical examination showed multiple swollen lymph nodes in the neck, and phlegm sounds could be heard in both lungs; (4) Laboratory examination: eosinophils were slightly increased in blood routine, inflammatory indicators were elevated, and the autoantibody profile was not obviously abnormal; (5) Chest CT: thickening of trachea and bronchial wall; bronchoscopic extensive mucosal nodules; bronchial mucosal pathology shows acute and chronic inflammation; (6) decreased saliva flow rate; Parotography shows that the branch ducts are not developed, and the distal ducts are cloudy and have slow emptying; labial gland pathology: focal lymphocytic infiltration; Although the patient was negative for SSA and SSB, the diagnosis of Sjögren's syndrome was established based on the medical history, parotid glandography and labial gland biopsy results, and the symptoms of dry mouth were relieved after glucocorticoid treatment, and the lymphadenopathy disappeared, supporting the diagnosis of Sjögren's syndrome. After treatment with glucocorticoids, respiratory symptoms and signs improved, lung imaging and bronchoscopic mucosal lesions improved, and from the perspective of treatment response, large airway lesions were considered to be related to the primary disease, but differential diagnosis should be made, such as granulomatosis with polyangitis (GPA), which can involve both the upper and lower respiratory tract and respond to glucocorticoid therapy. Yu Rong (otolaryngology): The patient had multiple mucosal protrusion-like lesions under laryngoscopy, obvious mucosal congestion and edema in the throat, and no mucosal bleeding ulcer changes; The vocal cords are well moved, and there is no thickening and edema of the vocal cords. Common diseases involving the throat include GPA, relapsing polychondritis, and sarcoidosis [1]. GPA pharyngeal involvement often presents with subglottic stenosis [2]; Recurrent polychondritis with laryngeal involvement may present with mucosal edema, vocal cord paralysis, and fixed subglottic stenosis [3, 4]; A small number of patients with sarcoidosis may develop granulomas nodular in the nasal passages, oropharynx, glottis, and larynx [5]. The patient's ANCA was negative, and the pathological findings of lip gland biopsy in the hospital did not support GPA; There are no typical manifestations of recurrent polychondritis such as arthralgia and airway collapse; Pathological biopsy of the labial gland does not support sarcoidosis. The diagnosis of Sjögren's syndrome is well defined, and there is insufficient evidence as to whether the pharyngeal manifestations can be explained by monism. Sjögren's syndrome has rarely been reported to involve the laryngeal mucosa. Biopsy is not considered due to the mild laryngeal lesions, the difficulty of biopsy, and the high risk of bleeding. Gao Li (Department of Radiology, Peking University First Hospital): The chest CT and tracheoscopy of this patient were mainly diffuse thickening of the large airways, involving the membranous area with calcification. The following diseases should be considered from the imaging manifestations: (1) tracheobronchial tuberculosis: although tracheobronchial tuberculosis is a common disease of central airway involvement, its imaging characteristics are segmental thickening of the tube wall and localized stenosis of the trachea or bronchi, which does not meet the characteristics of diffuse lesions in this patient [6]; Improvement of airway lesions after glucocorticoid therapy does not support the diagnosis of endobronchial TB. (2) GPA: There are several manifestations of tracheobronchial involvement of GPA, including subglottic stenosis and diffuse airway involvement [7, 8]. (3) Recurrent polychondritis: it is characterized by repeated attacks of cartilage inflammation of the ear, nose, peripheral joints, larynx, and tracheobronchial cartilage. Diffuse or focal airway involvement may be seen on imaging, with diffuse thickening of the airway wall without membranous involvement, and loss of the tracheal cartilage ring is typically seen [6]. (4) Ossifying tracheobronchiopathy: a rare benign lesion of the airway, characterized by abnormal trachea, bronchial submucosal ossification, and cartilage nodules protruding from the lumen, and generally does not involve the posterior airway wall [9]. (5) Airway amyloidosis: the patient has thickened airway wall with calcification, and airway amyloidosis should be considered in imaging. However, after short-term glucocorticoid therapy, the thickening of the tracheal and bronchial walls has significantly resolved compared with before, which is not consistent with amyloidosis. In February 2015, the chest CT scan was significantly better than before hormone therapy, indicating that hormone therapy was effective and GPA was more likely. Tian Xinlun (Department of Respiratory and Critical Care Medicine): The respiratory system of patients is mainly involved in the large airways, and from a clinical point of view, the following categories of diseases involving the large airways should be considered: (1) Infection: such as endobronchial tuberculosis, when the airway is involved, the airway wall can be thickened, distorted, and stenotized by imaging [10]. Endobronchial tuberculosis can be ruled out if there is no aetiological evidence during the diagnosis and treatment of the patient and there is improvement after hormonal therapy. (2) Sarcoidosis: 4%~6% of patients with sarcoidosis can have parotid gland enlargement, 7%~16% will have lacrimal gland enlargement [11, 12, 13, 14], and bronchial vascular bundle thickening can occur on imaging [15, 16]. The patient had no hilar and mediastinal lymphadenopathy, no granulomatous changes in labial gland and airway mucosal pathology, and the diagnosis of sarcoidosis was insufficient. (3) GPA: If there are manifestations of ear, nose, pharynx, and laryngeal involvement in the patient's medical history, combined with chest imaging manifestations, GPA should be considered. However, in addition to upper and lower airway involvement, common imaging findings in patients with GPA include nodules with or without cavitation, bronchiectasis, consolidation, and ground-glass opacities [17]. In this case, the patient had no evidence of renal and other system involvement, ANCA was negative, and there was no vasculitis in the pathological tissue, and the evidence of GPA diagnosis was insufficient. Min Peng (Department of Respiratory and Critical Care Medicine): The patient's history of patients with clear dry mouth, decreased salivary gland flow rate, and labial gland pathology suggestive of focal lymphocytic infiltrates was established according to the 2016 ACR-EULAR classification criteria for Sjögren's syndrome [18, 19]. Sjögren's syndrome is characterized by decreased lacrimal and salivary gland function with lymphocytic infiltration of exocrine glands (particularly lacrimal and salivary glands) [20, 21]. Clinical manifestations can be divided into two broad categories: exocrine gland involvement and extraglandular organ involvement [22]. In addition to causing dry eyes (keratoconjunctivitis sicca) and dry mouth (xerostomia), Sjögren's syndrome can affect extraglandular organ systems such as the skin, lungs, heart, kidneys, nerves, and hematopoietic system. 9%~20% of patients with Sjögren's syndrome have pulmonary involvement, including airway abnormalities such as airway serosis and follicular bronchiolitis [23, 24]. In this case, from a monistic point of view, the large airway lesions are secondary to Sjögren's syndrome. Tissue biopsy is required to rule out lymphoma and large airway amyloidosis or light chain deposition. Feng Rui'e (Department of Pathology): After being admitted to the hospital, the patient was sent for 4 biopsies of tracheal and bronchial mucosal tissues, and the pathological manifestations were all chronic inflammation, with unequal amounts of lymphocytes, plasma cells, eosinophils and a small number of neutrophils infiltrated under the microscope, no lymphofollicle formation, and the infiltrating inflammatory cells were mature in morphology and diverse in composition, and no lymphoma lesions, amyloidosis and light chain substance deposition were found. Airway involvement in Sjögren's syndrome is a common small airway lesion with follicular bronchioles or lymphocytic interstitial pneumonia, or nonspecific small airway inflammation [24, 25]; Pathologic involvement of the large airways has been reported rarely. In this case, the trachea and bronchi were non-specific inflammatory lesions, and it was difficult to determine the cause based on this pathology, and it was necessary to consider the clinical manifestations and other laboratory examination results. Shi Juhong (Department of Respiratory and Critical Care Medicine): This is a rare case of respiratory involvement in Sjögren's syndrome. The patient underwent repeated bronchoscopy during the course of seeking medical treatment, and because there was no characteristic hint of pathology, he was diagnosed with Sjögren's syndrome airway involvement after multidisciplinary discussion, and his condition improved after treatment. Lesions of the central airway in Sjögren's syndrome, particularly nodules visible on tracheoscopy, are rare. In 1989, Japanese scholar Miyazaki et al. [26] reported the first case of Sjogren's syndrome with tracheal and bronchial involvement, chest CT showed intraluminal masses in the trachea and left bronchi, multiple mucosal nodules on bronchoscopy, and shortness of breath symptoms and imaging improvement after prednisolone treatment. In 2017, Japanese scholar Hara et al. [27] reported that a 38-year-old female patient with Sjögren's syndrome presented with "cough and chest pain for one month", and multiple nodules in the trachea and main bronchi were seen on bronchoscopy. The patient had received prednisone 5 mg/day for a long time due to organizing pneumonia, and then added celecoxib for symptomatic treatment. After 5 months of treatment, repeated tracheoscopic nodules resolved. The treatment outcome of this patient was similar to that reported in previous cases, and his condition was stable after long-term follow-up. Lessons learned from the diagnosis and treatment process of this patient: (1) Sjögren's syndrome leads to diffuse bronchial wall thickening and multiple nodular bulges, which are rare and reported in the world, and need to be gradually recognized. (2) For large airway lesions, clinicians need to consider not only common diseases, but also rare diseases.
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