Idiopathic subglottic stenosis in a young female patient

Abstract

A previously healthy 30-year-old woman presented with 3 years of progressive shortness of breath and audible wheezing. One year prior to presentation, she developed a chronic non-productive cough. Pulmonary function testing revealed flattened inspiratory and expiratory peaks, characteristic of an extrathoracic fixed tracheal obstruction. Bronchoscopy confirmed subglottic stenosis (SGS). She had no history of intubation, tracheostomy or evidence of a systemic inflammatory illness. She was diagnosed with idiopathic SGS and referred for rigid bronchoscopy with balloon dilatation resulting in improvement in her symptoms.

Background

Subglottic stenosis (SGS) is a circumferential stenosis most often occurring below the vocal folds and involving the upper trachea. Thought of as an inflammatory process, it is commonly associated with intubation trauma. Other risk factors include morbid obesity and diabetes mellitus and may be associated with increased likelihood of intubation-related stenosis via chronic inflammatory states.^{1 2} The incidence of SGS after intubation can be as high as 10% but only 1%–2% of cases result in stenosis significant enough to cause symptoms.^{2 3} For stridor to be present, stenosis must progress to approximately 6 mm.⁴ Here, we report a case of idiopathic SGS (iSGS) in a young female patient. The patient lacked risk factors for airway stenosis such as airway trauma, active infection and did not display masses in or near the airway.

Case presentation

A woman in her early 30s was referred for evaluation of shortness of breath for the past 3 years. Initially, shortness of breath was noted only on exertion; however, it steadily increased to be present at even minimal levels of exertion. On a trip to Kenya associated with mountain climbing, the patient experienced severe worsening of her symptoms. In the year before presentation, she developed a non-productive cough. She also reported frequent respiratory illnesses, although she attributed these to occupational exposure as a family care resident physician. The patient reported that her patients and preceptors would comment on her audible wheezing as she hurried between examination rooms.

Further history revealed the presence of lingering myalgia over the past year. She denied prolonged intubation as well as symptoms of heart burn. She reported a history of light tobacco use ending several years prior and no active alcohol abuse. She worked as a family care resident physician in the final year of residency training.

Chest X-ray performed 7 months prior to presentation was unremarkable; however, pulmonary function testing at the time showed flattened inspiratory and expiratory peaks. An ENT (ears, nose, throat) evaluation noted swelling of the vocal cords suggestive of possible gastro-oesophageal reflux and started a trial of proton pump inhibitor (PPI) therapy with omeprazole. This did not improve her cough or shortness of breath and was discontinued.

Physical examination revealed a well-developed female in no acute distress. There was no cervical or supraclavicular lymphadenopathy. Auscultation of the cervical trachea revealed a rumbling sound. No wheezing, rales or rhonchi were noted over the lung fields. There was no digital clubbing or extremity oedema. Skin examination did not reveal evidence of rash.

Pulmonary function testing again demonstrated flattened inspiratory and expiratory peaks (figure 1). Flexible bronchoscopy confirmed the presence of SGS (figure 2).

Figure 1.

Flattening of the inspiratory and expiratory flow volume loops can be observed in this example. These blunted peaks indicate a fixed extrathoracic tracheal obstruction caused by subglottic stenosis. BD, bronchodilator; FVC, forced vital capacity; FEV1, forced expiratory volume in one second; FEF, forced expiratory flow; PEF, peak expiratory flow.

Figure 2.

A tight (~75%), slightly eccentric stricture in the subglottic space consistent with subglottic stenosis. Advancement of the flexible bronchoscope past the stricture resulted in dyspnoea and the procedure was aborted.

The patient was diagnosed with iSGS and referred for rigid bronchoscopy with balloon dilatation resulting in improvement in her symptoms. Tissue and culture from the procedure biopsy sample were unrevealing. The patient was concurrently evaluated for underlying collagen vascular disease for which there was no evidence.

Investigations

A chest X-ray was unremarkable. Previously performed laryngoscopy was suspicious for signs of oesophageal reflux by oedema of the vocal cords; however, the patient had no complaints of heart burn and PPI therapy did not improve the patient’s cough.

Pulmonary function testing showed no changes to total lung capacity (TLC), functional residual capacity (FRC), residual volume (RV), ratio of residual volume to total lung capacity (RV/TLC), and diffusing capacity for carbon monoxide (DLCO), however, it was significant for flattening of inspiratory and expiratory flow volume loops. These changes were not reversed with six inhalations (540 mcg) of an inhaled Β₂ agonist. These findings were consistent with an upper airway obstruction.

Erythrocyte sedimentation rate (ESR), C-reactive protein, antinuclear antibodies (ANA), antineutrophil cytoplasmic antibodies (ANCA), anti-Sjögren’s syndrome related antigen A (anti-SSA) and anti-Sjögren’s syndrome related antigen B (anti-SSB) antibodies, ACE, proteinase-3 and myeloperoxidase antibody screening returned negative.

Flexible bronchoscopy revealed tight, eccentric SGS. Tissue biopsy revealed partly denuded and attenuated respiratory mucosa with underlying chronic inflammation and collections of histiocytes. There was no evidence of neoplasia. Bacterial, fungal and mycobacterial cultures of the stenotic area obtained during rigid bronchoscopy were negative.

Differential diagnosis

Subglottic stenosis

By exclusion of other aetiologies, it was decided that the most likely explanation of this patient’s SGS was an idiopathic process. The long-standing myalgias suggested possible collagen vascular disease. However, her ANA, anti-SSA, anti-SSB and ANCA screens were negative and ESR was normal. The absence of traumatic intubation, history of respiratory failure and active tracheal infection further suggested SGS of an idiopathic aetiology.

Asthma

Wheezing, shortness of breath and coughing could be seen in patients with worsening obstructive lung disease such as bronchial asthma. Expiratory wheezes could be mistaken for inspiratory stridor. In the case of asthma or obstructive lung disease, spirometry would show an obstructive pattern without fixed tracheal obstruction. Forced expiratory volume in one second/forced vital capacity (FEV1/FVC) is characteristically decreased in obstructive diseases as well. Changes on spirometry would be reversible with bronchodilator challenge in asthma.

Neoplasia of trachea or thyroid

Certain neoplasms could present with mass effect and extrathoracic fixed tracheal obstruction. These may be observed on radiological studies or potentially present with more characteristic symptoms of the neoplasm (carcinoid syndrome/paraneoplastic syndromes/lung findings). The absence of intratracheal lesions on bronchoscopy precludes this diagnosis.

Outcome and follow-up

The patient was counselled on available treatments and wished to proceed with balloon dilatation of the airway. She was sent for consult with thoracic surgery and successfully underwent the procedure. One week after dilatation, the patient was seen by thoracic surgery and advised that repeat dilatations may be necessary depending on her course. If strictures became recurrent, tracheal reconstruction would be indicated. Three months post dilatation, she noted resolution of her shortness of breath, cough and voice changes. Her physical examination was unremarkable, and she had normalisation of her flow volume loop. At 9 months post single dilatation procedure, she continues to note resolution of symptoms. Her follow-up is ongoing.

Discussion

SGS is defined as upper airway obstruction from the glottis to the first two tracheal rings. Trauma resulting from tracheal intubation is the most common cause. High endotracheal tube cuff pressure and prolonged intubation time are likely related factors. SGS may also occur as a result of tracheostomy placement. Other causes include collagen vascular disease, tuberculosis, malignancy and tracheomalacia. Cases where no aetiology can be elucidated are deemed idiopathic, a rare phenomenon that was first described in 1972.^{5 6}

The reported incidence for iSGS is 1 in 400 000 patients.^{6 7} A literature search with PubMed using the terms ‘idiopathic subglottic stenosis’ yielded only 32 cases. The majority of patients diagnosed with iSGS are women between the ages of 20 and 50.1 2 6 7 Studies have shown iSGS can frequently present with gastro-oesophageal reflux disease (GORD), as well as hypertension, obesity, granulomatosis with polyangiitis, sarcoid and very rarely inflammatory bowel disease, among many others.2–4 6–9

The pathogenesis of SGS is thought of as a fibroinflammatory state leading to stenosis.^{1 9 10} There is evidence suggesting iSGS has a genetic component and demonstrates a degree of anticipation.⁹ The fibrosis has been characterised as keloidal and rich in CD8 cells.^{1 6 10} Due to the high predominance in young to middle-aged women, oestrogen has been suggested as playing a potential role in disease progression.^{3 6 10}

The presentation of SGS can appear non-specific and be difficult to diagnose without the aid of spirometry and bronchoscopy. Common symptoms on presentation include cough, dyspnoea, wheezing and stridor with worsening occurring as the degree of stenosis increases over time. In patients who have not been intubated or treated for respiratory failure, clinical suspicion of SGS is typically low and a diagnosis could be missed or mislabelled as asthma.¹¹ Disease progression can lead to compromise of the upper airway, a medical emergency which can lead to death. Pulmonary function testing may help distinguish between the two conditions: asthma will show an obstructive or normal pattern on spirometry, while SGS will show blunted inspiratory and expiratory peaks. Asthma may present with expiratory wheeze, while SGS will commonly present with inspiratory stridor. Both asthma and SGS may seem episodic or exacerbated on exertion and present with cough and shortness of breath. It is possible the incidence of SGS is higher due to misdiagnosis as asthma. iSGS may also present in systemic inflammatory states, such as granulomatous polyangiitis or sarcoidosis.

Modalities for treatment of iSGS include laser treatments, balloon dilatation and complete reconstruction of the airway.^{4 6} In severe or cases with rapid onset, tracheostomy may be used as a rescue modality.¹¹ First-line treatment of SGS is surgical dilatation of the stenotic airway, commonly via balloon dilatation during rigid bronchoscopy. Initial treatment failure may lead to tracheoplasty and complete reconstruction of the airway.⁴ Stenosis may reoccur after surgery in some cases and could recur faster in patients with diabetes.1–3 7 9 12 Simple strictures and web-like lesions can be definitively treated by balloon dilatation or laser therapy and some studies suggest aggressive treatment of underlying GORD if applicable; however, the efficacy of this is unclear.^{4 8 12} Due to the unclear benefit of GORD treatment for SGS and paucity of GORD symptoms in this case, no further evaluation with invasive oesophageal pH monitoring was done and PPI therapy was discontinued. Here, a single balloon dilatation was able to resolve the stricture without recurrence at over a year post dilatation.

In the case of iSGS, morbidity secondary to delayed diagnosis and treatment could be high. Clinicians must maintain a high degree of suspicion for this rare condition as well as conduct a thorough workup and history to rule out associated comorbid conditions.

Learning points.

• Subglottic stenosis can be an idiopathic process occurring independently of vasculitis, trauma, prior intubation and/or other inflammatory conditions.

• Idiopathic SGS can present similarly to obstructive lung diseases like asthma as well as tracheal masses.

• Fixed upper airway obstructions show flattened inspiratory and expiratory peaks on spirometry and can result in stridor, a finding not to be confused with wheeze.