Ryu, Jay H.

Background Constrictive (obliterative) bronchiolitis (CB) is an uncommon form of obstructive lung disease that can occur in patients with identifiable causes including connective tissue diseases (CTDs) as a form of lung involvement. We explored whether CB can be the presenting manifestation of CTD. Methods We identified 44 patients with cryptogenic CB and examined the presenting clinical, laboratory, and radiologic features, as well as their clinical course. Results The mean age at presentation was 60.5 (SD, 13.8) years and included 38 women (86%); 32 (73%) were never smokers. All patients presented for evaluation of dyspnea, commonly associated with cough. An obstructive pattern on pulmonary function testing was demonstrated in 86% of patients. On chest high-resolution computed tomography, nearly all patients manifested a mosaic attenuation pattern with air trapping on expiratory views, characteristic of CB. Bronchoscopic lung biopsy (n = 10) was usually nondiagnostic (90%), whereas all 5 surgical lung biopsies yielded evidence of CB. Serologic testing for CTD was positive in 19 patients (43%) and most commonly included antinuclear antibody, rheumatoid factor, and anti–cyclic citrullinated antibodies. Seven of these patients with positive serologic results were eventually diagnosed to have CTD. Connective tissue diseases included rheumatoid arthritis in 4 patients, Sjögren syndrome in 2, and undifferentiated CTD in 1 patient. Conclusions Nearly one-half of patients with cryptogenic CB manifest positive CTD serology, and some of these patients have CTD not previously diagnosed. These results suggest that CB can be the presenting manifestation of a CTD.

AbstractImmunoglobulin G4-related disease (IgG4-RD) is a systemic fibroinflammatory disorder that has been recognized to involve virtually any organ in the body and typically manifests mass-like lesions (tumefactive). Although initial reports of this disease (autoimmune pancreatitis [AIP]) were described in the Japanese population, it has since been reported worldwide. It is most commonly seen in adults of middle age or older, more often men than women. The pathogenesis of IgG4-RD is largely unknown, but genetic factors, microorganisms, and autoimmunity are thought to play important roles. Serum IgG4 concentration is elevated in the majority of patients with IgG4-RD but is a nonspecific finding. Characteristic histopathologic features include dense lymphoplasmacytic infiltrate, fibrosis (often in storiform pattern), and obliterative phlebitis. Lung involvement in IgG4-RD was first reported in 2004 in two patients with AIP and coexisting interstitial lung disease. Since then, a wide spectrum of intrathoracic involvement has been reported and includes not only parenchymal lung diseases but also pleural, airway, vascular, and mediastinal lesions. Thoracic involvement in IgG4-RD is often found incidentally during the workup of extrathoracic lesions but can sometimes be the presenting abnormality. The diagnosis of IgG4-RD requires correlation of clinical, laboratory, imaging, and histopathologic features. Glucocorticoids are the first-line therapy but other options including B cell depletion are being investigated. IgG4-RD is generally associated with an indolent clinical course and most patients improve with glucocorticoid therapy.

Common variable immunodeficiency (CVID) and selective immunoglobulin A deficiency (IgAD) often cause chronic lung disease, but the pulmonary pathologic features of these systemic diseases are poorly recognized by pathologists. It has been claimed that CVID cases show a characteristic combination of noncaseating granulomas-lymphoid proliferations termed granulomatous-lymphocytic interstitial lung disease (GLILD). We present 34 surgical lung biopsy cases of CVID and 4 of IgAD. Noncaseating granulomas were seen in 23/34 (68%) CVID and 2/4 (50%) IgAD cases. A statistically identical pattern of benign lymphoid proliferation was found in CVID and IgAD whether or not granulomas were present. Organizing pneumonia, sometimes considered a part of GLILD, was seen in 25/34 (74%) CVID and 2/4 (50%) IgAD cases and did not correlate with the presence of granulomas. On follow-up, 3 CVID patients died (only 1 of pulmonary disease), while 21 others are alive at 1 to 300 months with no difference by presence or absence of granulomas. Three IgAD patients with follow-up are alive. We conclude that CVID and IgAD are indistinguishable in surgical lung biopsies and a subset of both show patterns that would qualify as GLILD, while other cases lack granulomas but have identical patterns of lymphoid infiltration and organizing pneumonia. We suggest that GLILD is neither a specific nor a useful entity, and biopsies from CVID and IgAD patients should be diagnosed simply by microscopic pattern(s) observed. The prognosis of CVID with lymphoid infiltrates with or without granulomas in this series was good, contrary to claims in the literature about GLILD.