| Affiliation |
(AGL) Chairman, Department of Ophthalmology, The Methodist Hospital, Houston, Texas; Professor of Ophthalmology, Weill Cornell Medicine, New York City, New York; (JC) Class of 2023, Baylor College of Medicine, Houston, Texas |
| Transcript |
So today we're going to be talking about IgG4. And as you know immunoglobulin, Ig, and IgG, and the subclasses. And there are four subclasses and most of the normal IgG is actually 1, and 4 is actually a very small percentage of the immunoglobulin subclass IgG. However, at some point, some type of antigen is encountered inside of a tissue, where an antigen presenting cell will take up that antigen, interact with the T cell, and that T cell talks to the B cell and says, "Take this antigen and make an antibody." And when that antibody is made, it can be defined by subclass. Usually, these are different based on some difference in the hinge region. And for IgG4, the subclass restriction, something happens abnormally in this interaction that causes this B cell to continue to produce more IgG4. It's not clear exactly why that happens. And the reason it's important to us clinically is IgG4-related disease. A lot of diseases that we called "idiopathic" in the past are now turning out to be IgG4. And so, for neuro-ophthalmology, that is idiopathic orbital inflammatory syndrome or orbital inflammatory pseudotumor. So, when we see a patient who has proptosis, pain, ophthalmoplegia, and their imaging study shows an inflammatory lesion in the orbit, even though that could be idiopathic orbital inflammatory syndrome, we still have to worry about IgG4. And the only way to make the determination, ultimately, is with pathology. Because we cannot see the IgG4, we have to use special immunohistochemical stains to identify that IgG4 is present in that specimen. And even though you can measure the IgG4 in the serum, it's not reliable enough to make the diagnosis. And most of the diagnostic criteria require a very high percentage of IgG4 to be present and only your pathologist can answer these questions, but generally it's a high number, like 40%, have to be IgG4. So, we need to have the "path" to do the stains, the immuno stains, for IgG4, before we blame it on no cause, idiopathic. Now there are some clinical features that suggest it might be IgG4. As opposed to orbital inflammatory pseudotumor, which is normally unilateral, IgG4 disease can be bilateral or unilateral. And IgG4 disease can be chronic, as opposed to acute and monophasic, and recurrent. IgG4 disease also can be painless, especially if it's the sclerotic, fibrotic form, where there's not a lot of inflammation. But ultimately, the only way to make a diagnosis is with a biopsy and that biopsy has got to have special staining looking for IgG4. So, when we're dealing with IgG4-related disease, what we really are thinking about is, "Is this ‘-itis' confined to the orbit or not?" And so, every subspecialty of medicine has their own version of idiopathic orbital inflammatory pseudotumor. But their inflammatory pseudotumor might be in the salivary glands, miculates, or in the thyroid gland, Riedel's thyroiditis, or retroperitoneal fibrosis, or the pulmonary version of it, or the cardiac version of it, or the renal version of it, every subspecialty in medicine has their own idiopathic "-itis" and some of those have eponyms. And so, the really important feature of making the diagnosis of IgG4-related disease is to look for it in other organ systems. So, in a patient who has orbital inflammatory disease, before we call it idiopathic, we must look in the past medical history and what we're looking for is "-itis" in other organ systems, orbital inflammatory disease that was unexplained in idiopathic in other organ systems. We're going to do the "path" and look for the IgG4 staining in the specimen. You can do the serum, but it is not as good, and the "path" usually requires a very high percentage of IgG4. Doesn't change the treatment in the short-term, which is steroids, but it does change our vigilance for looking for the disease elsewhere, because IgG4-related disease can really affect any organ system. And so, a lot of disorders that I used to call idiopathic weren't. And you should be thinking about IgG4-related disease in those patients. |
