“While there is a growing body of case work on IgG4-related disease, people still find it a revelation that IgG4-related disease is actually a form of vasculitis.”
The epidemiology of IgG4-related disease as well as its management, clinical outcomes, and healthcare utilization remain poorly understood nearly 20 years after it was first recognized as a unified disease in 2003.
As John Stone MD. MPH, Edward Fox Chair of Medicine and Professor of Medicine at Harvard Medical School discussed during one of the three talks he presented at the American College of Rheumatology 2022 Annual Meeting, “IgG4-related disease really should be classified as a variable-vessel vasculitis, that can impact very small blood vessels all the way through to the largest in the body - the aorta.”
“While there is a growing body of case work on IgG4-related disease, people still find it a revelation that IgG4-related disease is actually a form of vasculitis,” Dr. Stone continues. “In fact, cases of IgG4-related disease are often misdiagnosed as cancers, as the inflammation can be easily confused with a tumor.”
“Looking back to the German medical literature from the 1890’s, you can see drawings of patients who clearly had IgG4 related disease, yet the condition wasn’t recognized as a unified multi-organ disease until less than 20 years ago.”
In his talks, Dr. Stone stresses that under the microscope, IgG4-related disease can look very similar to other conditions, complicating diagnosis. IgG4-related disease has two important mimics: Dacryoadenitis and Granulomatosis with PolyAngiitis (GPA), with the latter being a “Clinical Doppelgänger” for IgG4-related disease. However, he stresses that while histological staining and storiform fibrosis fail to differentiate, serology can. There are other diseases that also look similar under the microscope, but are very different clinically.
“IgG4-related disease is a very slow disease, indolent and sub–acute, and on the other side of the spectrum is Castleman's disease – a raging hurricane of a disease, which can kill patients very quickly. Histopathologically, they have very similar appearances but clinically, they behave very differently.”
He also identifies that while pediatricians rarely hear about IgG4-related disease, it does occur in children, “In pediatric patients, IgG4-related disease tends to involve the eyes. Sometimes the disease looks just like it does in adults when it occurs in children.” He continues “the most florid case of IgG4-related disease that I've seen, was in a sixteen year-old boy who had multi-organ disease and classic manifestations of the disease in all of those organs.”
In addition to his talks on new treatments for IgG4-related disease in adults and children, Dr. Stone presented a poster with colleagues from Massachusetts General Hospital and Sanofi discussing the results of a retrospective observational study that indicate the disease is at least as common as ANCA-associated vasculitis and systemic sclerosis. However Dr. Stone cautions the prevalence is likely underestimated due to a persistent lack of awareness about the disease.
The researchers conducted a retrospective observational cohort study using the Optum Clinformatics claims database from 1/1/2009-12/31/2021 and used a validated algorithm requiring ICD codes, IgG subclass tests, and treatment to identify 524 IgG4-related disease cases and a matched set of 5,240 comparators.
The poster, entitled “The Epidemiology, Clinical Outcomes, and Healthcare Resource Utilization of IgG4-Related Disease Among Commercially Insured People in the United States” highlights data showing glucocorticoids were the most frequently prescribed class of therapy, and that IgG4-related disease cases vs. comparators had significantly more outpatient and emergency room visits, and hospitalizations. Many of the co-morbidities that patients with IgG4-related disease experience, it turns out, are related to their glucocorticoid treatment. The IgG4-related disease patients also had significantly greater pharmacy costs and an increased risk of death compared with the comparator group.
These findings support the need for greater awareness of the disease so diagnosis rates can be improved, coupled with a need for more effective steroid-sparing therapies for IgG4-related disease.