ReviewTracheobronchial involvement of relapsing polychondritis
Introduction
Relapsing polychondritis (RP) is a rare systemic disease which can be disabling and life-threatening. It is characterized by recurrent bouts of inflammation followed, in some cases, by degeneration and deformation involving the cartilage of the ears, nose, larynx, and tracheobronchial tree [[1], [2], [3]]. Other structures that consist of proteoglycans can also be involved, such as the eyes, heart, and inner ear. There may also be manifestations of vasculitis.
A recent cluster analysis identified three separate phenotypes: a hematological form (in 10% of cases), a respiratory form (in 25% of cases), and a mild form with a good prognosis (approximately 65% of cases) [4]. Tracheobronchial involvement is the hallmark of the respiratory phenotype of RP, which was classically considered to carry a poor prognosis. In this large series, patients with such a phenotype received more intensive treatment and suffered from more infections but no patient died of airway collapse or obstruction due to RP, which has been a significant cause of mortality in older series. Another study confirmed that patients with lower respiratory tract involvement have different characteristics [5]. These results show that patients with associated tracheobronchial involvement are distinct from others in terms of clinical characteristics, therapeutic management, and disease evolution [4].
Here, we review the current knowledge of respiratory tract involvement and its management in RP, with special emphasis on the most recent data.
Section snippets
Epidemiology
RP chiefly affects middle-aged adults, with a slight female predominance, but cases have been reported in the very young and very elderly [6]. All ethnic groups are affected. In the US, the estimated incidence of RP is 3.5 per million inhabitants per year [7] and the prevalence among Department of Defense beneficiaries is 4.5 per million inhabitants [8]. A more recent population-based cohort study found an incidence of 0.71 per million inhabitants per year [9]. The prevalence of respiratory
Clinical manifestations of tracheobronchial involvement
Respiratory involvement is inaugural in 10% of cases [14,15]. Airway involvement occurs early during the course of the disease, at a mean of 2.5 years after diagnosis [4].
Laryngeal involvement is manifested by pain and soreness of the larynx, above the thyroid gland. Dysphonia, aphonia, or hoarseness of the voice are possible. Laryngeal involvement may result in laryngomalacia or laryngeal stenosis, responsible for inspiratory dyspnea [14,16].
Tracheobronchial involvement leads to inflammation
Diagnostic and classification criteria
There are no validated classification or diagnostic criteria for RP. The diagnosis of RP is based on clinical evidence and physician experience [1,14,17]. The most commonly used criteria are the Michet criteria [2], but they are for classification. Patients are classified as having RP if they fulfill two major criteria or one major and two minor criteria. Laryngo-tracheal involvement is a major criterion of this classification. It is now commonly accepted that the exclusion of differential
Imaging
The main imaging method used to diagnose RP is computed tomography (CT), with end-inspiratory and dynamic expiratory scans. A chest CT scan, including an expiratory acquisition, should be routinely performed at diagnosis, even in the absence of respiratory symptoms. It should be repeated as necessary during the evolution of the disease. The cervical portion of the trachea should be included. Thus, the acquisition should start below the vocal cords. Expiratory CT scan images can be acquired at a
Pulmonary function testing
Pulmonary function testing must be performed at diagnosis and repeated annually to detect airway impairment and estimate its progression. It should not be performed during a superimposed infection. Spirometry, volume-flow curves, and the measurement of upper airway resistance may show early involvement in asymptomatic patients [10,26]. Obstructive disease (FEV1/FVC <70%) and reduced exercise capacity (walk test desaturation and decreased distance walked) should be sought.
Obstructive disorders
Fibroscopy
Fibroscopy should be performed in patients with respiratory symptoms, especially when interventional endoscopy is necessary. It can evaluate mucositis, define the severity (narrowing or stenosis), and allow the dynamic assessment of possible collapse (expiratory maneuver or coughing). However, it should be performed with care because of increased morbidity and mortality associated with the procedure: risk of acute flare-up of the disease, leading to edema of the respiratory or supraglottic
Pathophysiology of respiratory impairment
An immune origin, involving humoral and cellular immunity, is suspected [14,17,28], as:
1) there is an associated autoimmune disease in up to 30% of cases, 2) chondritis lesions contain a CD4+ T-cell lymphocyte infiltrate and plasmocytes, as well as immune deposits, 3) autoantibodies directed against type II collagen are detected in approximately 30% of cases, or against other types of minor collagen (IX and XI) or cartilage proteins, such as oligomeric proteins of the cartilaginous matrix
Histology
Histological specimens of the anterior tracheal cartilage are sometimes obtained during fibroscopy but there is no histological specificity. If performed, there is perichondral lympho-plasmocytic cellular infiltration of the cartilage, with the loss of basophilic staining of the cartilaginous matrix, corresponding to the loss of proteoglycans. The cartilage is gradually replaced by fibrous tissue. These abnormalities evolve from the periphery to the center and predominate at the junction
Treatment of relapsing polychondritis respiratory disease
Therapeutic management is empirical. It is not based on therapeutic trial data but mainly the physician's experience and the data from a few case series and involves a collaboration between the pulmonologist and the rheumatologist or internist. The goal of treatment is to control symptoms and maintain airway stability [10].
Evolution and prognosis
The evolution of the disease is progressive, consisting of flare-ups, leading to possible permanent destruction of the cartilage [1]. Some symptoms may persist between flare-ups.
Overall RP survival has improved considerably. It was 55% at 10 years in 1986 [2], 94% at 8 years in 1998 [1], and 83% at 10 years in the most recent study [4]. The improved prognosis is partially due to the availability of interventional treatments, but RP-related morbidity and mortality are still high, particularly in
Conclusions
Over the past few years, it has become clear that there are distinct forms of RP in terms of clinical characteristics, therapeutic management, and disease evolution. Overall, RP survival has improved considerably. However, more complete characterization of the different subsets and their pathophysiological features are needed to establish more appropriate therapeutic strategies based on the patients' disease characteristics and prognosis.
Contributors
N.d.M. and X.P. wrote the initial draft. D.D., C.L., J.D., N.C.C., L.M., G.C., and M.P.R. reviewed the manuscript and made substantial contributions to the discussion of the content. All authors reviewed and/or edited the manuscript before submission and agreed to its publication.
Funding
The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Patient consent
Not required.
Provenance and peer review
Not commissioned; externally peer reviewed.
Declaration of Competing Interest
None declared.
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