A Spotlight on IgG4-Related Disease

Is Elevated Serum IgG4 Concentration Diagnostic of IgG4-RD?

No, a diverse array of other conditions can be associated with elevations in the serum IgG4 concentration. However, the higher the concentration of IgG4 in the blood, the greater the suspicion for IgG4-RD, particularly if the patient’s clinical manifestations are consistent with this disorder. Our patient’s serum IgG4 concentration was 2,020 mg/dL (normal<121 mg/dL).

As is true with many serologic assays for newly described conditions, tests for serum IgG4 concentrations have been problematic in some circumstances. One recently described problem with serum IgG4 assays relates to the “prozone phenomenon.” The prozone effect can occur in conditions of large analyte excess when assays such as nephelometry, which are dependent upon immune complex formation, are used. The prozone effect can lead to major underestimates of the quantity of the analyte in question.¹¹

Although the prozone effect accounts for some spuriously low, false-negative results, it seems clear that a significant minority of patients—perhaps fewer than 20% of those who have not been treated—have normal serum IgG4 concentrations in the setting of diagnostic histopathology and immunostaining findings in involved organs.

Are Radiologic Examinations Specific for IgG4-RD?

Radiologic findings in IgG4-RD may mimic those of other diseases. The most common example of this is the tendency of IgG4-RD to mimic malignancies in their presentation as pseudotumors. This fact usually makes histopathological confirmation of the diagnosis essential.

Because IgG4-RD was first recognized in the pancreas, the radiology of IgG4-RD is described most thoroughly in that organ. In the proper clinical setting, the finding of a diffusely enlarged, “sausage-shaped” pancreas with peripancreatic stranding is sometimes sufficient for the diagnosis of type 1 autoimmune (IgG4-related) pancreatitis. A bulging contour of the pancreas is seen in most patients. Peripheral inflammation or fibrosis of the pancreas can be detected on computed tomographic (CT) scanning as a peripheral rim or peripancreatic stranding. In contrast to pancreatic cancer, IgG4-related type 1 autoimmune pancreatitis is usually associated with homogeneous contrast enhancement throughout the pancreas. Pancreatic duct stenosis, obstruction, or irregular narrowing may be observed on imaging studies, and temporary stent placement is required for some patients. Calcifications and pseudocyst formation within the pancreas are unusual in IgG4-RD, in contrast to other forms of chronic pancreatitis.¹²

Figure 4: Pericarinal mass in a patient with IgG4-RD.

B: Histopathology of this tumoral lesion, revealing the classic lymphoplasmacytic infiltrate and storiform fibrosis of IgG4-RD.

C: Immunostaining of the lung lesion for IgG4. The IgG4:total IgG ratio in this sample was 0.88 (IgG staining not shown).

A full understanding of the pulmonary manifestations of IgG4-RD continues to evolve. However, from the standpoint of the CT appearance of lesions, five major types have been described.¹³ These are nodules, ground-glass opacities, alveolar-interstitial lesions, bronchovascular thickening, and pleural thickening. An example of a pericarinal mass associated with thickening of the bronchovascular bundle and compression of the right mainstem bronchus is shown in Figure 4 (above), along with its corresponding histopathology and immunostaining features.