Rare Community Profiles is a Patient Worthy article series of long-form interviews featuring various stakeholders in the rare disease community, such as patients, their families, advocates, scientists, and more.
White Paper Discusses Access Barriers in IgG4-Related Disease (IgG4-RD)
In medicine, certain conditions receive extensive attention, research, and treatment options. Others remain obscure, with limited understanding and few to no treatments available. IgG4-related disease (IgG4-RD) falls into the latter category, presenting a complex challenge for both patients and healthcare providers. Despite its severity, IgG4-RD has received minimal attention in broad medical discourse. Dr. John H. Stone, MD, MPH, a Professor of Medicine at Harvard Medical School and rheumatologist at Massachusetts General Hospital, saw his first patient with IgG4-RD in 2007. He shares:
“At that point, I had been a rheumatologist for years and had never knowingly seen a patient with IgG4-RD, though, in retrospect, I now know I missed some. It reinforced to me how many individuals lacked adequate and understanding care. In the 17 years since, I have focused my career on IgG4-RD.”
In 2024, Dr. Stone, a member of the Alliance for Patient Access and founder of IgG4ward, co-authored a white paper entitled “Addressing Access Barriers for IgG4-RD Patients.” This paper underscores the challenges faced by individuals living with IgG4-RD when attempting to receive appropriate care, including barriers such as limited understanding and awareness among healthcare providers, diagnostic delays, and telehealth and utilization management.
In his recent interview with Patient Worthy, Dr. Stone discusses IgG4-RD, the findings from the white paper, and the need for better support and research within this patient community. His advocacy serves as a call to action for increased collaboration and better efforts to solve the challenges faced by those with IgG4-RD. By working together to increase awareness, enhance research, and improve access to care, we can transform the landscape for this disease.
What is IgG4-RD?
IgG4-RD is an immune-mediated disease characterized by an abnormal accumulation of immune cells that produces IgG4, an antibody. This causes inflammation and tumor-like mass formation in organs such as the meninges, lacrimal and major salivary glands, thyroid gland, bile ducts, pancreas, kidneys, lungs, and heart. As Dr. Stone explains:
“This disease can affect multiple organs, though it may only affect one. It is indolent, or slow-moving, which is why it causes so much damage. People don’t realize that they’re sick but, while they might not have symptoms, they have raging inflammation in their pancreas or other organs. This damage typically begins many months, and in many cases, years, before symptom onset when the diagnosis can be made.”
One of the challenges of diagnosing IgG4-RD stems from the fact that different organ involvement begets different symptoms. Some individuals with salivary gland involvement may visit a rheumatologist for swollen parotid or lacrimal glands. An individual with pancreatic or bile duct dysfunction or painless jaundice (yellowing of the skin and eyes) would visit a gastroenterologist; these symptoms are usually associated with cholangiocarcinoma or pancreatic cancer, which means a patient might be referred to an oncologist.
Blocked urine flow or altered kidney function lands someone a visit to a nephrologist, and cranial nerve dysfunction and headaches lead to neurologist visits. Other symptoms can include weight loss, fatigue, bulging eyes, large vessel vasculitis, abdominal pain, and shortness of breath, requiring visits to other specialists. Says Dr. Stone:
“Diagnosing IgG4-RD reminds me of an old legend of physicians in the Middle Ages. They were blind and trying to figure out the animal in front of them, an elephant. One physician felt the tail and another the trunk, leading them to their own conclusions. In IgG4-RD, each subspecialist sees the disease through a different lens, which can make it difficult to diagnose. This is worsened by the fact that IgG4-RD mimics many other conditions. Patients are often told they have cancer based on mass-forming lesions in the pancreas, lungs, or eyes. IgG4-RD is mistaken for rheumatologic diseases. My first patient was referred to me for Sjogren’s syndrome. IgG4-RD may also resemble forms of vasculitis like granulomatosis with polyangiitis. Improving awareness of this disease could significantly benefit patient outcomes.”
Another diagnostic challenge stems from the fact that IgG4-RD was not recognized as a unique condition until 20 years ago—it only received its ICD10 code in October 2023. Many practicing physicians did not learn about IgG4-RD in medical school or subsequent training. Because of this, the medical profession is still in its early stages of learning about this condition.
Managing IgG4-RD
Steroids are typically used to manage IgG4-RD symptoms and reduce inflammation. Doctors may also prescribe off-label rituximab, a B lymphocyte-targeting therapy. Dr. Stone shares that there has been a significant amount of grade B evidence in its efficacy, which raises hope that other therapies, like one currently in clinical testing, will be effective. Non-biologic DMARDs such as methotrexate and azathioprine may also be leveraged to reduce the number of steroids someone has to take. Says Dr. Stone:
“One of the wonderful things about IgG4-RD is that it is treatable. It typically responds well to therapies.”
However, Dr. Stone also explains that steroids might not be the best therapy for this patient population. He notes:
“IgG4-RD tends to affect middle-aged to elderly individuals who may already have comorbidities that make the use of steroids a challenge. When a patient with a damaged pancreas gets put on prednisone, it can cause newly-onset or worsening diabetes. We very badly need an approved therapy for IgG4-related disease and access to that therapy.”
According to Dr. Stone, this is on the horizon:
“What’s surprising about IgG4-RD is that this disease, although it is an orphan disease, is actually quite common. Specialists of every type see people with this disease. Because of the unappreciated size of this population and the insufficiencies of existing therapies, it is really important to have an approved therapy that people can get access to. We’re on the verge of having the first approved medicine for IgG4-RD that targets B lymphocytes that target CD19. This is now completing its Phase 3 clinical trial, the first of its kind in this disease state. Results will be shared this fall during the American College of Rheumatology and this drug could be the first to achieve regulatory approval.
“Addressing Access Barriers for IgG4-RD Patients”
As a Senior Statesman for IgG4-RD and the Executive Chairman of the IgG4ward Foundation, the first and only organization dedicated to IgG4-RD advocacy, research, and support, Dr. Stone was asked to participate in discussions on barriers to care with the Alliance for Patient Access, another organization with which he is a member.
Through these discussions emerged multiple concerns about IgG4-RD: diagnostic challenges, the lack of approved therapies, unmet medical needs, standards-of-care, mental health. It soon became clear that there needed to be a comprehensive paper that sought to discuss these access barriers and empower physicians to provide a better quality-of-life to people with this disease.
One important consideration within the paper was mental health. There is an emotional dimension to rare disease and chronic illness. People often face medical gaslighting and the resulting medical PTSD, deal with prolonged periods of waiting for diagnosis, and are isolated from the greater community. In IgG4-RD specifically, says Dr. Stone:
“People are often told they have advanced and inoperable cancer with only a few months to live. Once they have the diagnosis, they realize they don’t have cancer, but they also realize that there is almost no information on IgG4-RD written at a level that patients can understand. So they go from being terrified that they’re going to die to confused because they don’t know what to make of their disease.”
In part, this is why Dr. Stone launched IgG4ward!—to provide a wellspring of valuable information for patients in a way that they can understand. The foundation offers information on clinical trials and research, IgG4-related disease facts and other helpful resources, and an online community that understands what patients are going through—and you can connect through fireside chats, caregiver groups, and monthly educational offerings. All information shared is carefully curated by physician experts and an international expert advisory board comprising global physicians from various specialties. Says Dr. Stone:
“With IgG4ward!, I want to offer the best and most correct info early on. Soon, if all goes according to plan, we’ll have new and improved therapies that will greatly inform patient journeys. In the meantime, I want to remind people to stay strong. Hope is not just on the way—hope is here.”
You can read the white paper from the Alliance for Patient Access here.
