laryngopharyngeal reßux, a newly recognized disease that produces local symptoms and laryngeal changes caused by the reßux of gastric contents into the upper aerodigestive tract [26]. Unlike classic gastroesophageal reßux, esophagitis, heartburn, or complaints of regurgitation are rare symptoms. Treatment options include gastric acid suppression and lifestyle modiÞcations.

19.3.5 Liver Involvement

The liver is affected in a small number (5%) of patients with pSS. These patients present with elevated liver enzymes and antimitochondrial antibodies [27, 28]. The liver biopsy discloses histopathologic lesions of stage I primary biliary cirrhosis. In these patients, ursodeoxycholic acid can be of some beneÞt. Autoimmune hepatitis can also occur, requiring treatment with prednisolone and azathioprine [29].

19.3.6 Lung Involvement

Manifestations from the tracheobronchial tree are frequent but rarely clinically important. They can present either with dry cough secondary to dryness of the tracheobronchial mucosa (xerotrachea) or dyspnea due to airway obstruction or interstitial lung disease. The major Þnding of lung involvement is small airways obstruction, which is frequently associated with mild hypoxemia. Chest radiography shows mild interstitiallike changes, and high-resolution computed tomography (CT) of the lung in patients with abnormal chest radiography reveals wall thickening at the segmental bronchi. Transbronchial and/or endobronchial biopsy specimens discloses peribronchial and/or peribronchiolar mononuclear inßammation [30]. Non-speciÞc interstitial pneumonia (NSIP) is also a common pathologic Þnding [31]. However, severe interstitial disease in SjšgrenÕs syndrome is rare and is appreciated only after a complete functional and radiological evaluation of the patient. In most patients, the use of β(beta)-agonists and corticosteroids demonstrated little beneÞt. In rare

cases of interstitial lung disease, prednisolone administration, with or without an immunosuppressive agent (azathioprine), might be a viable option.

19.3.7 Kidney Involvement

Clinically signiÞcant and biopsy-documented renal disease is observed in approximately 5% of patients with pSS [32]. Two forms of renal involvement have been described, interstitial nephritis or glomerulonephritis. Subclinical involvement of the renal tubules can be seen in one-third of patients, as attested by an abnormal urine acidiÞcation test. Renal biopsy typically reveals interstitial lymphocytic inÞltration. Most patients present with hyposthenuria and hypokalemic, hyperchloremic distal renal tubular acidosis, reßecting interstitial inÞltration and destruction by lymphocytes. Distal tubular acidosis may be clinically silent, but if left untreated, signiÞcant renal tubular acidosis may lead to renal stones, nephrocalcinosis, and compromised renal function. Such patients may present with recurrent renal colic and/or hypokalemic muscular weakness. Less commonly, SjšgrenÕs syndrome patients have proximal tubular acidosis with FanconiÕs syndrome. Hypokalemic hyperchloremic acidosis, the most serious manifestation of tubular dysfunction, can be treated with oral potassium and sodium bicarbonate [33, 34].

Membranous or membranoproliferative glomerulonephritis in SjšgrenÕs syndrome has been described in few patients. Cryoglobulinemia, associated with hypocomplementemia, is a consistent serological Þnding in these cases [35]. Interstitial nephritis is usually an early feature of the syndrome, whereas glomerulonephritis is a late sequel [32]. Glomerulonephritis is mainly treated with prednisolone and/or pulse intravenous cyclophosphamide. In cases of treatment of refractory disease, caution is required, however, because the use of cytotoxic agents is associated with a 100-fold increase in the incidence of lymphoma in patients with SjšgrenÕs syndrome [36].