196 |
C.P. Mavragani et al. |
Table 14.1 Type of respiratory system involvement in Sjögren’s syndrome (SS) (lymphoproliferative disorders are not included)
Upper airway disease |
Rhina sicca |
|
Recurrent sinusitis |
|
Xerotrachea |
Lower airway disease |
Lymphocytic bronchitis/bronchiolitis |
|
Bronchial hyperresponsiveness |
|
Diffuse panbronchiolitis |
Interstitial lung disease |
Non specific interstitial pneumonia (NSIP) |
|
Usual interstitial pneumonia (UIP) |
|
Cryptogenic organizing pneumonia (COP) |
|
Follicular bronchiolitis/cysts/bullae |
|
Lymphocytic interstitial pneumonia (LIP) |
Pleural disease |
Mainly in SS associated with other autoimmune diseases |
|
|
14.1Introduction
Isolated cases of lung involvement in Sjögren’s syndrome (SS) were first reported in the early 60s [1]. Since then an extensive number of reports have attempted to characterize lung involvement, often with conflicting data. Principally interstitial [2–5] to mixed [6, 7] or purely obstructive respiratory patterns [8] have been described, with frequencies that range from 9% to 75% [3, 4]. The observed variability partly reflects differences in definitions and varying applications of diagnostic criteria among studies, the sensitivity of modalities employed for the detection of lung abnormalities, and the inclusion of patients with concomitant pulmonary disease such as that resulting from smoking or other primary autoimmune conditions. Despite the differences observed across studies, one consistent theme is that the pulmonary manifestations of patients with primary SS differ from those associated with secondary SS. As examples, pleural effusions and fibrosis, found commonly in patients with secondary SS, rarely occur in pSS [9, 10]. Such manifestations are generally attributed most appropriately to the underlying primary connective tissue disease (CTD) [11].
In this chapter, we focus on pulmonary involvement in pSS, with particular attention to the two major clinicopathological disease phenotypes: airway and interstitial lung disease (ILD) (Table 14.1). Pulmonary arterial hypertension and bronchusassociated lung lymphoma (BALT) are discussed elsewhere in this book (Chaps. 13 and 33, respectively).
14.2Airway Disease
14.2.1Overview
Mucus secretion from the lining epithelial cells of the upper respiratory tract is one of the major innate natural barriers against inhaled pathogens. In the context of an autoimmune exocrinopathy, impaired secretions from the epithelial cells can result
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197 |
in reduced moistening, nasal crusting, epistaxis, and recurrent episodes of sinusitis. Furthermore, dryness of the throat, persistent hoarseness, and foreign body sensation presumably due to lymphoid infiltration of the nasal cavity and pharynx can also occur [3, 12]. Lymphocytic infiltration of the laryngeal, tracheal, and bronchial exocrine glands in a similar way to that observed in the salivary and lachrymal exocrine glands of pSS patients results in desiccation of the respiratory tree and is mainly manifested by a commonly persistent and irritating dry cough.
Isolated dry cough, described first by Henrik Sjögren in his original report, is a frequent complaint in pSS, reported in up to 50% of patients [3], even in those without radiographic findings or pulmonary function impairment [13]. Although the origin of cough was attributed to desiccation of the mucosa of the tracheobronchial tree (xerotrachea) [3, 4], identifiable abnormalities by means of rhinoscopy or indirect laryngoscopy are detected in only 20% of patients [14, 15]. In the absence of concomitant features, incorrect diagnoses such as asthma or bronchitis are often made prior to the diagnosis of pSS [3].
Although some reports have suggested increased prevalence of bronchiectasis in pSS [16–18], presumably resulting from plugging of the respiratory tract by inspissated secretions [4, 12], the majority of studies failed to document such an association [3, 13, 19, 20].
14.2.2Pathology
The principal histopathological abnormality of airways is a peribronchial and/or peribronchiolar infiltration by CD4-positive T-lymphocytes, leading to small airway obstruction. These cells are predominant in the lamina propria outside the bronchial submucosal glands [21]. Hyperplasia of goblet cells and bronchial glands by morphometric analysis was also disclosed in autopsies from six patients with pSS [22].
14.2.3Imaging Studies
Radiological studies in patients with pSS revealed the presence of reticular and reticulonodular abnormalities, reminiscent of an interstitial disorder [3, 4]. However, on the basis of high-resolution CT (HRCT) lung findings, Papiris et al. have suggested that this pattern actually corresponds to thickened bronchioles probably resulting from peribronchial and/or peribronchiolar mononuclear inflammation [13]. Predominant bronchiolar abnormalities have also been reported in studies involving non-smoking pSS patients by Franquet et al. and Taouli et al., with frequencies ranging from 32% to 65%, respectively [18, 23]. A mosaic pattern of lung attenuation or air trapping was identified on expiratory HRCT scans, corresponding to bronchiolar disease [23]. Finally, evidence of bronchiectasis on HRCT has been reported in up to 38% of patients with pSS in the study of Koyama et al. [16].