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CASE SERIES
Ahead of print publication  

Subglottic stenosis as a presentation of various rheumatic diseases


 Department of Rheumatology and Clinical Immunology, Sir Gangaram Hospital, New Delhi, India

Date of Submission05-Feb-2022
Date of Acceptance06-Mar-2022
Date of Web Publication27-Aug-2022

Correspondence Address:
Bhavya Chintala,
Room No. 2208A, SSRB Block, Sir Gangaram Hospital, Old Rajender Nagar, New Delhi
India
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/injr.injr_26_22

  Abstract 


The subglottic space at the cricoid level is the narrowest part of the airway. Subglottic stenosis (SGS) is generally benign and may be due to a variety of diseases, but post-intubation injury is the most frequent cause. Other causes are tracheal infections including bacterial tracheitis, tuberculosis, histoplasmosis and diphtheria, and collagen vascular diseases including granulomatosis with polyangiitis, relapsing polychondritis, etc., SGS may be a presenting complaint in rheumatological disorder. In this case series, we shall discuss patients with rheumatic diseases presenting with SGS.

Keywords: IgG4 related disease, relapsing polychondritis, subglottic stenosis, vasculitis



How to cite this URL:
Chintala B, Duggal L, Jain N, Gupta M. Subglottic stenosis as a presentation of various rheumatic diseases. Indian J Rheumatol [Epub ahead of print] [cited 2022 Oct 3]. Available from: https://www.indianjrheumatol.com/preprintarticle.asp?id=354875




  Introduction Top


Subglottic stenosis (SGS) is defined as narrowing of the airway immediately below the vocal cords.[1] In patients with SGS, clinical symptoms of stridor, hoarseness, and dyspnea require urgent evaluation and may be severe to require tracheostomy. Endo bronchial inflammation and stenosis occurs less frequently than subglottic disease but may present with similar clinical manifestations. SGS can be a manifestation of various rheumatological disorders such as ANCA vasculitis, relapsing polychondritis, and IgG4-related disease.[2] In rare cases, SGS can be a presenting features of these rheumatological diseases. In this article, we are discussing cases presenting with SGS and later diagnosed with rheumatic disease.


  Case Reports Top


Case 1

A 41-year-old male presented with complaints of red discoloration and pain of both eyes for 2 months with hoarseness of voice and shortness of breath, pain and redness of both eyes, sudden in onset, simultaneously involving both eyes. The pain was deep boring in nature, severe in intensity, and not associated with vision loss, double vision. He also had complaint of hoarseness of voice since 1 month which was sudden in onset, associated with an episode of stridor, not associated with dysphagia. Shortness of breath was sudden in onset, Modified medical research council (MMRC) grade III. Other clinical history was not significant. On examination, there was erythema of bulbar conjunctiva on nasal side in both eyes with no systemic involvement. In laboratory investigations, hemogram, liver function test (LFT), and renal function test were normal, ANA, myeloperoxidase (MPO), and PR3 were negative and C3, C4 were normal. Computed tomography (CT) scan neck and thorax showed circumferential wall thickening in subglottic region with luminal narrowing. Aorta showed calcification and thickening in arch and descending aorta. Positron emission tomography (PET) CT scan revealed mildly fluorodeoxyglucose (FDG) avid diffuse circumferential mural thickening involving aorta and its major branches, likely large vessel vasculitis [Figure 1]. Biopsy from subglottic tissue was taken which showed focal dense infiltrates composed of lymphocytes with scattered plasma cells positive for CD 138. IgG4 cells –10–12/hpf and IgG4/IgG >40%. Diagnosis of IgG4-related disease was made and IV pulse steroid and IV cyclophosphamide were given. Due to COVID-19 pandemic, the patient refused for IV cyclophosphamide. He was shifted to oral 100 mg/day of the above drug which he took for 3 months and was lost to follow-up. 12 months after treatment, relapse occurred and the patient shifted to Rituximab.
Figure 1: Positron emission tomography computed tomography imaging of patient with IgG4 related disease with Subglottic stenosis and large vessel involvement. Findings were suggestive of mildly fluorodeoxyglucose avid diffuse circumferential mural thickening involving aorta and its major branches, likely inflammatory (Large vessel vasculitis) and fluorodeoxyglucose avid diffuse soft tissue thickening of bilateral vocal cords and subglottic region causing mild luminal compromise

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Case 2

A 40-year-old male patient, resident of Tanzania, was admitted with complaints of hoarseness of voice for 1½ years and difficulty in breathing since 6 months. He had a history of Bullous pemphigoid 8 years ago for which he consulted a dermatologist in Kenya and took dapsone for 6 years. In 2017, in view of breathing difficulty and throat swelling, tracheostomy was done. ENT examination showed congested laryngeal mucosa. Hemogram, renal, and LFT were normal. Blood, urine, and ET cultures were negative. Indirect laryngoscopy was suggestive of SGS. In immunological investigations, p and c ANCA and ANA were negative, serum IgG (1214 mg/dl) and IgG4 levels (98 mg/dl) were normal. Chest X-ray was normal. CT neck was done which showed hypopharyngeal mass. PET CT scan showed FDG avid asymmetrical thickening with luminal compromise involving glottic and subglottic with mild FDG avid axillary and cervical Lymph nodes. Tissue biopsy from the glottic region showed mature plasma cell infiltrate with fibrosis, IgG4 cells >10%, IgG4/Plasma cells 50%–55% of plasma cells, suggestive of IgG4 disease, with no evidence of epithelioid granuloma or malignancy [Figure 2]. On the basis of clinical picture and histological findings, diagnosis of probable IgG4-related disease was made and methylprednisolone 24 mg was started which was gradually tapered. Injection rituximab 1 g was given which was repeated after 15 days and 6 months. The patient's symptoms improved with treatment.
Figure 2: Biopsy from subglottic patient in IgG4-related disease showing mature plasma cell infiltrate with fibrosis, IgG4 cells- 10–15/hpf, IgG4 cells 50%–55% of plasma cells

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Case 3

A 35-year-old female presented with fever, hoarseness of voice, and breathing difficulty since 1 month. ENT examination showed laryngeal edema. Hemogram, renal, and LFTs were normal. Blood, urine, and ET cultures were negative. Indirect laryngoscopy was suggestive of SGS. On clinical examination, the patient had saddle nose deformity and floppy ear with stridor. Contrast-enhanced computed tomography neck and thorax revealed glottis and SGS with circumferential wall thickening of trachea with intraluminal collapse suggestive of relapsing polychondritis [Figure 3]. Biopsy from nasal tissue was taken which showed inflammatory infiltrate with chondrocytes and fibrosis which was consistent with a diagnosis of relapsing polychondritis. In view of breathing difficulty and SGS, tracheostomy was done. The patient was started on IV pulse steroid, along with methotrexate which was switched to azathioprine due to persistence of symptoms. She was also given injection Infliximab. She did well on treatment for 1 year after which similar symptoms recurred. Infliximab was stopped and IV cyclophosphamide was given. After 2 years, again relapse occurred, then injection tocilizumab (anti-interleukin [IL] 6) was started. The patient is currently well on tocilizumab therapy.
Figure 3: Clinical image showing floppy ears and saddle nose deformities secondary to relapsing polychondritis

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Case 4

A 36-year-old male patient presented with breathing difficulty since 2 months. On examination, inspiratory stridor was present. Indirect laryngoscopy was suggestive of SGS. In laboratory investigations, anti PR3 was elevated, MPO was negative. Biopsy from subglottic tissue was in favor of a diagnosis of granulomatous with polyangiitis. In view of breathing difficulty and SGS, tracheostomy was done. IV pulse steroid and rituximab was started. The patient responded to treatment and is currently on maintenance RTX therapy.

Case 5

A 45-year-old female patient presented with breathing difficulty and throat pain since 1 month. Chest X-ray and electrocardiogram were normal. Video laryngoscopy was suggestive of SGS. In laboratory investigation, anti-PR3 was elevated, MPO was negative. Biopsy from subglottic tissue was in favor of diagnosis of Granulomatous with polyangiitis. IV pulse steroid and rituximab was started. The patient responded to treatment and is currently on maintenance therapy.

Case 6

A 62-year-old male patient presented with breathing difficulty, throat pain, and since 20 days. Indirect laryngoscopy was suggestive of SGS. In laboratory investigation, anti-PR3 and MPO were elevated. Biopsy from subglottic tissue was in favor of diagnosis of granulomatous with polyangiitis. IV pulse steroid and rituximab were started. The patient responded to treatment and currently on maintenance RTX therapy.


  Discussion Top


SGS is defined as narrowing of the airway immediately below the vocal cords and is the most common manifestation of tracheobronchial granulomatosis with polyangiitis (GPA), with an estimated frequency of 16%–23%.[3] In patients with SGS, clinical symptoms of stridor, hoarseness, and dyspnea require urgent evaluation and may be severe enough to necessitate tracheostomy. IgG4-related disease has been observed in nearly every organ, including the biliary system, thyroid, salivary glands, kidneys, lungs, skin, lymph nodes, and orbital tissues.[4] Airway involvement has been described in the nasal cavity, trachea, and lungs and seldom in the larynx, with no reports of isolated pharyngeal involvement. Chronic antigenic stimuli, such as those provided by microbial antigens, might explain the oligoclonal expansion of IgG4-positive plasma cells.[5] Laryngotracheal involvement in RP is the most serious complication that is observed in 50% of the patients and may lead to a life-threatening condition.[6] The most common cause of death is laryngotracheal stenosis associated with lung infections or severe respiratory insufficiency that may be observed in 10%–50% of the patients. In our case series as discussed above 6 patients presented with SGS, 3 (50%) were diagnosed with GPA, 2 (33%) had IgG4 related disease, and 1 was diagnosed with relapsing polychondritis, and 2 patients were tracheostomized. Steroids were given in all patients, rituximab was given in 4 patients, cyclophosphamide in 2 patients, and IL 6 inhibitor in 1 patient. All patients responded to treatment. This is the only case series to our knowledge with SGS in various rheumatic diseases. Majority of studies were published with granulomatosis with polyangiitis, Kaitlin A Quinn et al., described tracheobronchial disease in 962 patients with GPA and evaluated the utility of dynamic expiratory CT to detect large-airway disease.[7] Guardiani et al. demonstrated the presentation and clinical course of SGS, in particular the development of concurrent airway lesions, in patients with GPA in 35 patients.[8] Horta et al. described clinical features and treatment of patients with SGS in 4 patients.[9] Peña et al. reviewed clinical features and treatment of patients with SGS in 56 patients.[10] Of all 56 cases of SGS, 48 (86%) had a history of previous tracheal intubation, and only 8 (14%) had different nonneoplastic obstructive processes such as scleroma, direct injury, hamartoma, and amyloidosis. Atienza-Mateo et al. reported A patient with IgG4-RD affecting the larynx that presented as SGS.[11] Taşlı et al. published a series of 3 cases of Relapsing polychondritis with isolated tracheal stenosis.[12]


  Conclusion Top


Rheumatic diseases are some of the rare causes of SGS. Most cases are reported with granulomatosis with polyangiitis, other causes are relapsing polychondritis, IgG4-related disease, etc., It is important to diagnose these conditions early as they require aggressive immunosuppression with or without surgical intervention.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient (s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Gnagi SH, Howard BE, Anderson C, Lott DG. Idiopathic subglottic and tracheal stenosis: A survey of the patient experience. Ann Otol Rhinol Laryngol 2015;124:734-9.  Back to cited text no. 1
    
2.
Aravena C, Almeida FA, Mukhopadhyay S, Ghosh S, Lorenz RR, Murthy SC, et al. Idiopathic subglottic stenosis: A review. J Thorac Dis 2020;12:1100-11.  Back to cited text no. 2
    
3.
Langford CA, Sneller MC, Hallahan CW, Hoffman GS, Kammerer WA, Talar-Williams C, et al. Clinical features and therapeutic management of subglottic stenosis in patients with Wegener's granulomatosis. Arthritis Rheum 1996;39:1754-60.  Back to cited text no. 3
    
4.
Stone JH, Yoh Zen MP, Deshpande V. IgG4- related disease. N Engl J Med 2012;366:539-51.  Back to cited text no. 4
    
5.
Reder L, Della-Torre E, Stone JH, Mori M, Song P. Clinical manifestations of IgG4-related disease in the pharynx: Case series and review of the literature. Ann Otol Rhinol Laryngol 2015;124:173-8.  Back to cited text no. 5
    
6.
Rapini RP, Warner NB. Relapsing polychondritis. Clin Dermatol 2006;24:482-5.  Back to cited text no. 6
    
7.
Quinn KA, Gelbard A, Sibley C, Sirajuddin A, Ferrada MA, Chen M, et al. Subglottic stenosis and endobronchial disease in granulomatosis with polyangiitis. Rheumatology (Oxford) 2019;58:2203-11.  Back to cited text no. 7
    
8.
Guardiani E, Moghaddas HS, Lesser J, Resta-Flarer F, Blitzer A, Bhora F, et al. Multilevel airway stenosis in patients with granulomatosis with polyangiitis (Wegener's). Am J Otolaryngol 2015;36:361-3.  Back to cited text no. 8
    
9.
Horta-Baas G, Hernández-Cabrera MF, Catana R, Pérez-Cristóbal M, Barile-Fabris LA. Subglottic stenosis in granulomatosis with polyangiitis (Wegener's granulomatosis): Report of 4 cases. Reumatol Clin 2016;12:267-73.  Back to cited text no. 9
    
10.
Peña J, Cicero R, Marín J, Ramírez M, Cruz S, Navarro F. Laryngotracheal reconstruction in subglottic stenosis: An ancient problem still present. Otolaryngol Head Neck Surg 2001;125:397-400.  Back to cited text no. 10
    
11.
Atienza-Mateo B, Díaz de Terán-López T, Gómez-Román J, Sánchez L, Mons-Lera R, Rubio-Suárez A, et al. Atypical presentation of immunoglobulin G4-related disease as subglottic stenosis: A case-based review. Rheumatol Int 2021;41:1161-7.  Back to cited text no. 11
    
12.
Taşlı H, Birkent H, Gerek M. Three cases of relapsing polycondritis with isolated laryngotracheal stenosis. Turk Arch Otorhinolaryngol 2017;55:77-82.  Back to cited text no. 12
    


    Figures

  [Figure 1], [Figure 2], [Figure 3]



 

 
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