Zachary S Wallace, MD: What’s New in IgG4 Disease?

Rheumatology Network interviewed Zachary S Wallace, MD, to discuss his presentation Congress of Clinical Rheumatology (CCR) East presentation “What’s new in IgG4 disease? An Approach to the Diagnosis & Management of IgG4-RD.” Wallace is Assistant Professor of Medicine at Massachusetts General Hospital.

Zachary S Wallace, MD: IgG4-related disease is an increasingly recognized condition. It first started to be recognized in the early 2000s, but obviously it's been around for many years. It has many different types of manifestations and can affect different organs. It was only in the early 2000s, that people started to kind of piece together all of these different things and put them under an umbrella of what would become known as IgG4-related disease. And like many of our other rheumatic diseases, it can affect nearly any organ, the most common ones being the salivary glands, the pancreas, the kidneys, and other sites as well. But what it does when it affects these areas is it causes these lesions that are characterized as having a lot of inflammation. What's somewhat unique is that it has a lot of inflammation that's significant for IgG4 positive plasma cells, but it also has a lot of fibrosis. They kind of look like tumors or cancers in these organs, and it can cause damage to the organ,and a lot of different types of symptoms.

Rheumatology Network: What are the key points that you will be discussing in your presentation?

ZW: We’re going to review the typical manifestations of the disease and how clinicians can better recognize or think about the diagnosis and understand when they should be thinking about diagnosing someone with IgG4-related disease. We're going to talk a little bit about some of the laboratory features and pathology features that you typically see in IgG4-related disease, and we're going to spend some time going over the ACR classification criteria for IgG4-related disease. Those were published a couple of years ago, but are increasingly used in trials, different studies, and clinically to help guide clinicians as they're evaluating patients for this diagnosis. They’re a useful framework for thinking about the differential diagnosis and making sure that you're considering alternative explanations for the patient's symptoms when they present. We’re going to spend time discussing treatment approaches and how we manage IgG4-related disease these days and what’s on the horizon.

RN: Can you tell me a bit more about the treatment approaches?

ZW: Typically, the most commonly used treatment is glucocorticoids or steroids. Most people treat for about 3 months or so. Steroids are very effective in this disease. Over 90% of patients will have a great response to steroids and if they don’t it's usually because their diseases very fibrotic. The challenge is that steroids have a lot of side effects. They lead to a lot of toxicities, especially in this population where people tend to be middle aged or older. Oftentimes men already have pancreatic disease, they're already at risk for diabetes or have diabetes. Adding steroids on top of that just leads to a lot of complications.

Also, this is a disease that tends to relapse. What we find is that even when you use steroids and you taper them down, a lot of patients within that first year of tapering down or off their steroids, a great portion of them are going to flare. Many people still use steroids, here and around the world, but we have had a lot of experience using B cell depletion, particularly with rituximab. Oftentimes, we use rituximab upfront, and we can treat without any steroids. Rituximab is pretty effective, but it has not been evaluated in a large clinical trial head-to-head with steroids and it's not FDA-approved for this indication.

There's a lot of challenges getting retirement for these patients. There are 2 kind of strategies, other things that are used are methotrexate and other common medicines that might be used to treat this. But there's a lot of enthusiasm and energy now and to identify other treatments and really investigate what might be effective for IgG4-related disease. There have been some phase 2 trials looking at other drugs, like a novel drug that targets plasma blasts. We have a trial going on right now using efalizumab, which is similar to rituximab in a number of ways. There's a lot of exciting things on the horizon that identify what the best treatment approach would be to get IgG4-related disease into remission.

RN: What are the takeaways or clinical significance for rheumatologists?

ZW: Some takeaways would be that we're probably all seeing IgG4-related disease, but we may not be recognizing it or diagnosing it. You have to think about it and really look for it, but it is there. The other message is that there's not a diagnostic finding for IgG4-related disease. Elevated serum IgG4 concentrations and IgG4 positive plasma cell infiltrates and tissue are not specific to the to the disease and about a third of patients actually have a normal serum IgG4 concentration, so it's easy to get thrown off by those observations.

The other take home message would be that steroids are very effective but have a lot of toxicities. There are alternative therapies that may be as effective or more effective than steroids.