IgG4-Related Lung Disease and Miscellaneous Vasculitis



IgG4-Related Lung Disease and Miscellaneous Vasculitis


Eunhee S. Yi, M.D.

Marie-Christine Aubry, M.D.



IgG4-Related Lung Disease


Introduction

IgG4-related disease (IgG4-RD) is a recently recognized fibroinflammatory condition that typically presents as tumefactive lesions involving one or more organs showing dense lymphoplasmacytic infiltrate containing increased IgG4-positive plasma cells, storiform fibrosis, and nonnecrotizing vascular inflammation on histologic examination.1 IgG4-RD may affect the lung as well as virtually any body site. Pulmonary manifestations of IgG4-RD are varied, with an involvement of not only the lung parenchyma but also the pleura, the mediastinum, and the thoracic lymph nodes. In a cross-sectional study, 16 of 114 patients (14%) with IgG4-RD were found to have lung or pleural involvement, in the presence or absence of other extrapulmonary manifestations such as type I autoimmune pancreatitis (AIP).2,3


Clinical Features

Patients with IgG4-RD involving the lung have similar epidemiologic features to those with extrapulmonary disease with an average age of 69 years and male predominance (70% to 80%).3 Approximately 50% of patients with pulmonary IgG4-RD have respiratory symptoms including cough, dyspnea on exertion, and chest pain, while the remaining patients present with incidentally found radiologic abnormalities in the absence of significant respiratory symptoms.2,4,5,6 Constitutional symptoms such as high fever and remarkable weight loss are uncommon. Overall, the clinical manifestations in pulmonary IgG4-RD patients are nonspecific.2,4,5,6 No known risk factors such as smoking or inhalation exposure have been identified in these patients.


Radiologic Findings

Patients with pulmonary IgG4-RD reveal various patterns of abnormalities. Four types of intrapulmonary lesions in chest CT scan have been reported5,7: (1) thickening of bronchovascular bundles and interlobular septa, (2) solid nodules resembling primary lung cancer, (3) interstitial involvement, and (4) round-shaped ground-glass opacities. The rounded opacities may vary in size from subcentimeter to > 5 cm in diameter. The opacity can manifest as solid or ground-glass attenuation. The margin of the opacity may be smooth or irregular and spiculated. In some patients, patchy consolidation and ground-glass opacities may suggest organizing pneumonia.5,8,9,10 In others, reticular opacities and honeycombing may predominate similar to the findings seen in nonspecific interstitial pneumonia or idiopathic pulmonary fibrosis, respectively.5,11,12 Infiltrates along bronchovascular bundles and interlobular septa may raise the suspicion of sarcoidosis especially when accompanied by thoracic lymphadenopathy.5 Some patients may present with pleural effusion or nodular lesions involving the pleura.5,13 Mediastinal and/or hilar lymphadenopathy is not uncommon and may be seen with or without parenchymal lung involvement.2,14,15,16,17,18 On 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) scanning, abnormal FDG uptake can be observed in IgG4-related lung lesions and thus will not help distinguish IgG4-related lung nodule or mass from lung cancer.


Laboratory Abnormalities

Serum IgG4 level is elevated in the majority of patients with pulmonary as well as extrapulmonary IgG4-RD.2,5,11,17,19 A serum level of IgG4 > 135 mg/dL, the upper normal used in many laboratories, has been reported in 1,586 of 1,883 (84%) of patients in a large-scale study.19 The mean serum IgG4 level was 760 mg/dL.19 Sensitivity and specificity of elevated serum IgG4 level with respect to IgG4-RD are not precisely known in pulmonary IgG4-RD or in IgG4-RD in general. It has been well recognized, however, that there is a broad spectrum of diseases that have elevated serum IgG4 level above 135 mg/dL without evidence of IgG4-RD.20 Thus, one should be aware of the fact that merely elevated serum IgG4 level is neither sufficient nor necessary for the diagnosis of IgG4-RD.

Recent studies have purported that plasmablast concentration in peripheral blood on flow cytometry could be a useful biomarker not only for the initial diagnosis but also for following disease activity of the patients with IgG4-RD.21,22 By flow cytometry, plasmablast concentration can be measured by gating CD19lowCD38+CD20-CD27+ cells. Concentration of IgG4+ plasmablasts can be also determined by flow cytometry.21 Additional studies are required, however, before plasmablast concentration by flow cytometry can be widely used as a clinical test.

Mild to moderate eosinophilia is found in 34% of IgG4-RD patients, but this finding is nonspecific. Elevated C-reactive protein (CRP) levels were reported in 23% of cases; even in the setting of multiorgan disease, however, elevations in serum CRP are generally modest and are less pronounced than in erythrocyte sedimentation rate. Polyclonal hypergammaglobulinemia (total serum IgG levels >1,800 mg/dL) was reported in 313 of 510 (61%). Serum IgE level was elevated in 58%.7,23,24,25,26,27,28 No specific autoantibody has been described consistently in patients with IgG4-RD, but the presence of nonspecific antibodies prevalent to other immune-mediated conditions is not uncommon; antinuclear antibody (ANA) and rheumatoid factor (RF) are found in nearly 30% and 20%, respectively. Hypocomplementemia is quite common especially in the patients with renal involvement by IgG4-RD.20

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Aug 19, 2016 | Posted by in CARDIOLOGY | Comments Off on IgG4-Related Lung Disease and Miscellaneous Vasculitis

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