Diagnostic Approach to the Complexity of IgG4-Related Disease

Abstract

IgG4-related disease (IgG4-RD) is a systemic disease characterized by the infiltration of IgG4-bearing plasma cells and, more importantly, distinctive histopathological features: storiform fibrosis, obliterative phlebitis, a lymphoplasmacytic infiltrate, and mild-to-moderate tissue eosinophilia. The diagnostic approach is complex and relies on the coexistence of various clinical, laboratory, and histopathological findings, none of which is pathognomonic in and of itself. IgG4-related disease should be suspected in patients presenting with unexplained enlargement or swelling of 1 or more organs or tissue organs. Four laboratory abnormalities often provide initial clues to the diagnosis of IgG4-RD: peripheral eosinophilia, hypergammaglobulinemia, elevated serum IgE levels, and hypocomplementemia. Elevated serum IgG4 levels provided critical information in identifying the first cases of IgG4-RD, but recent studies have reported substantial limitations to the measurement of serum IgG4 concentrations, precluding reliance on serum IgG4 concentrations for diagnostic purposes. In contrast, new studies have suggested a promising role of flow cytometry studies in the diagnosis and longitudinal management of IgG4-RD. Demonstration of the classic histopathological features of IgG4-RD remains crucial to diagnosis in most cases, and biopsy proof is preferred strongly by most disease experts before the initiation of treatment. Of note, the multiorgan nature of IgG4-RD was first established in 2003. This review intends to provide most recent knowledge about the clinical, laboratory, radiological, and pathological characteristics of IgG4-RD that may guide the physician to establish an early diagnosis. We searched PubMed and MEDLINE for relevant articles published between January 1, 2000, and November 1, 2014, using the search terms IgG4 and IgG4-related.

Immunoglobulin G4-Related Disease and the Lung

“…18,19 Similarly, the density of IgG4 1 plasma cells in involved organs varies and influences the quantitative cutoff values used for number of IgG4 1 plasma cell per high-power field and IgG4 1 /IgG 1 cell ratio in the histopathologic diagnosis of IgG4-RD. 20,21 …”

“…Patients with IgG4-RD commonly present with multiorgan manifestations, although single-organ involvement is noted in approximately 40% of patients. 3,4,7,8,12,21,22 During the clinical course of active IgG4-RD, various organs may become involved metachronously.…”

“…However, bronchoscopic or transthoracic needle biopsy may sometimes yield features suggestive of IgG4-RD while allowing exclusion of competing diagnoses. 2,20,21 Although histopathologic data are important in confirming the diagnosis of IgG4-related lung disease, lung or pleural biopsy may not be necessary in achieving this diagnosis if an extrapulmonary organ has already been biopsied to confirm the presence of IgG4-RD. In the absence of another more likely explanation for the intrathoracic lesion, the diagnosis of IgG4-RD can be assumed in most such cases.…”

“…Although serum IgG4 level is often elevated (>135 mg/dL) in patients with IgG4-RD, this laboratory finding is not an adequately sensitive or specific for diagnostic purposes. 3,21,[61][62][63] Serum IgG4 level has been reported to be elevated in 50% to 95% of patients with active IgG4-RD. 8,61,63,64 Conversely, only 10% to 20% of patients with an elevated serum IgG4 level in clinical practice have IgG4-RD.…”

Efficacy between high and medium doses of glucocorticoid therapy in remission induction of IgG4‐related diseases: a preliminary randomized controlled trial

“…[1][2][3] Due to the short duration of understanding of the disease, there is no uniform standard or guideline for treatment of IgG4-RD. It is widely accepted that patients with IgG4-RD are generally sensitive to glucocorticoid, with organ swelling reduced or disappearing after treatment, along with the decreasing of serum IgG4 levels.…”