Sjögren syndrome (SS) is a chronic autoimmune disorder of the exocrine glands and extraglandular organs, in which the dryness of the eyes (xerophthalmia) (Figures 23.1a, b, c, d and 23.2a, b, c) and mouth (xerostomia) (Figure 23.3) dominate along with symp- toms of polyarthritis (Figure 23.4). It is an autoimmune exocrinopathy with accumula- tion of lymphocytes and plasma cells; the similar perivascular lymphocytic infitrates could be found in various organs, including the lungs. It can be encountered alone (primary Sjögren syndrome) or in the presence of another autoimmune disorder (60%
of cases), most frequently rheumatoid arthritis. Women are more frequently affected than men. Rheumatoid and anti-nuclear factors are positive in a majority of patients;
the finding of anti-Ro (SS-A) and anti-La (SS-B) antibodies being specific for SS (Figure 23.5). Despite extensive research, the pathogenesis of SS remains unknown. Certain dis- turbances of the immune system (i.e., B-cell hyperreactivity and enhanced levels of B cell–activating factor/B-lymphocyte stimulator) probably play a central role in this entity. Whether this is a primary abnormality or the result of predisposing factors remains uncertain.
Pulmonary manifestations of SS are numerous and frequent but rarely cause severe symptoms. (Table 23.1). The airways are often involved; trachea (xerotrachea) and bronchi due to lymphocytic infiltrates of tracheobronchial submucose. It causes hoarse- ness and cough, and complications such as atelectasis, recurrent pneumonias, and bronchiectasis.
Interstitial lung disease is uncommon in primary SS but more common in secondary disease, probably as the complication of accompanying diffuse connective tissue disease lung changes. The most frequent histopathological finding is lymphoid interstitial pneu- monia (LIP) (Figure 23.6a, b).
Plain radiograph shows linear or reticular changes in about 22% of patients (Figure 23.7). HRCT reveals ground-glass opacities and interlobular thickening in about 58% of SS patients (Figure 23.8a, b).
Bronchoalveolar analysis reveals lymphocytic alveolitis with some granulocytes. Lung biopsy should be performed if minimal doubt exists toward the malignant lymphopro- liferative alteration. It is usually suspected on the grounds of radiological finding of solitary or multiple round opacities, alveolar infiltrates, or hilar or mediastinal lymphadenopathy.
The therapy of pulmonary manifestations of SS includes steroidal and nonsteroidal anti-inflammatory agents, disease-modifying agents, and cytotoxic agents. Therapy should also include topical agents to improve moisture and decrease inflammation.
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Figure 23.1. Dry eye. Typically, patients complain of sandy, gritty feeling, soreness and scratchiness. Other symptoms include heaviness of the lids, foreign body sensation, discom- fort while blinking, stinging, and photophobia. Most prevalent are intolerance of longer watching of TV or working on computer, irritation worsening in air-conditioned spaces (cars, offices) and during colder season of the year. Also, there may be marked difference between the extent of symptoms and clinical signs, which point to dry eye. Dry eye does not have to be red, while patients may still have dry eye symptoms needing treatment. Clinical appearance of decompensated dry eye; the dry eyes are red and inflamed (a); advanced kera- toconjunctivitis (b). Most frequent clinical appearance of dry eye: no or minimal redness (c). A lachrymal gland biopsy showing typical lymphocytic infiltration in a patient with Sjögren syndrome (d).
Figure 23.2. Primary test for tear film dysfunction is TBUT (tear break-up time) test, as tear film instability, together with hyperosmolality, are two signs common to all forms of dry eye. If TBUT is lower than 10 s, tear film is considered unstable. TBUT: tear film stained by sodium fluorescein breaks up (a). If the tear film is established to be unstable by TBUT, Schirmer test is performed. In case of values lower than 10 mm of wetted paper in 5 min, diagnosis of hyposecretory dry eye is established. Schirmer test values above 10 mm/5 min indicate tear hyperevaporation as the cause of dry eye. (b)
Figure 23.2c. Cornea stained by sodium fluorescein: in dry eye staining is typically located in lower (more exposed) portions of cornea.
Figure 23.3. Dry mouth can present without or with parotid glands enlargement; in this patient the parotids are enlarged and hardened. The characteristic skin teleangiec- tasis are also seen.
Figure 23.4. Painful and inflamed joints are frequent complaints in patients with Sjögren syndrome; the ankles are painful and swollen.
Figure 23.5. Antibodies directed against SS-A and SS-B. Coarse to fine speckles in inter- phase cells (Hep-2 cells; Euroimmun, Lubeck, Germany; objective ×40).
Table 23.1. Pleuropulmonary manifestations of Sjögren syndrome (SS).
Sjögren Syndrome Frequency
Parenchymal disease
Lymphoid interstial pneumonia +++
Nonspecific interstitial pneumonia +
Bronchiolitis obliterans organizing pneumonia +
Usual interstitial pneumonia ±
Amyloidosis +
Recurrent bronchopneumonia ++
Airway disease
Atrophic rhinitis ++
Xerostomia, xerotrachea +++
Chronic bronchitis ++
Bronchiolitis ++
Bronchiectasis +
Pleural disease
Pleural disease ±
Pulmonary vascular disease
Pulmonary hypertension ±
+++, common; ++, fairly frequent; +, occasional; ±, rare.
Figure 23.6. Histopathological finding of the lung biopsy in a patient with SS and ILD shows lymphocytic interstitial pneumonia; malignant alteration can proceed so if there is a slightest possibility of such event, the transtracheal or open lung biopsy is advised. Marked lymphoid aggregates in the bronchial wall are seen (a). A lung biopsy sometimes shows bronchiolitis, as well as numerous lymphocytes (b).
Figure 23.7. Chest radiograph in a patient with SS shows linear and reticular pattern, superimposed with patchy alveolar opacities, predominantly in the lower half of the lung. Right pneumothorax as a complication of transbronchial biopsy procedure is seen.
Figure 23.8. HRCT scan shows ground-glass pattern and thickening of the interalveolar septa in geographical distribution (a). Another case of SS showing peripheral intralobular and interlobular thickening with peripheral peribronchovascular micronoduli (b).
