Key milestones in IgG4-RD research and care highlighted at recent meeting
Through a blend of personal anecdotes, historical insights, and scientific breakthroughs, Dr. Arezou Khosroshahi highlighted the strides made in understanding, diagnosing, and treating IgG4-related disease (IgG4-RD) during a presentation at the 2024 IgG4ward Jamboree.
A Personal Journey into IgG4-RD
Dr. Khosroshahi’s journey began in 2008 during her rheumatology fellowship at Massachusetts General Hospital (MGH), under the mentorship of Dr. John Stone. Early in her training, a case involving submandibular gland swelling and subsequent biopsy revealed similarities to autoimmune pancreatitis, sparking her interest. A subsequent case involving aortic dissection and inflammation further deepened her exploration into IgG4-RD.
Her investigations led to the first case of IgG4-RD at MGH being treated with rituximab, setting the stage for the disease’s recognition and treatment. This case, published in The Lancet, catalyzed the establishment of an IgG4-RD clinic and a patient registry at MGH.
The Historical Path
IgG4-RD has a long but fragmented history, Dr. Khosroshahi said. The earliest descriptions date back to the 1800s, with peculiar cases of glandular swelling documented in Germany. Over the decades, scattered publications described symptoms resembling IgG4-RD, including autoimmune pancreatitis in the 1960s and the association of elevated IgG4 levels with pancreatic inflammation in 2001 by Japanese researchers.
However, it wasn’t until 2011 that a unified nomenclature—IgG4-related disease—was adopted following a global symposium spearheaded by Dr. Stone and Dr. Khosroshahi. This event brought together experts from diverse disciplines to consolidate knowledge and foster collaboration.
Challenges in Recognition and Diagnosis
Dr. Khosroshahi highlighted the challenges in diagnosing IgG4-RD, citing its diverse presentations, including glandular swelling, pancreatic involvement, and retroperitoneal fibrosis. The disease’s rarity—affecting approximately 5.3 per 100,000 people—compounds these challenges.
Adding to the complexity, IgG4-RD often mimics other conditions, leading patients to seek care from various specialists before a diagnosis is confirmed. Despite advancements, there remains no definitive blood test or imaging study for IgG4-RD, necessitating a combination of clinical expertise, pathology, and imaging.
Progress and Future Directions
Significant progress has been made in understanding IgG4-RD. Since 2011, international collaborations have produced consensus guidelines for diagnosis, management, and classification. Clinical trials, including those for rituximab, have advanced treatment options, with the hope of FDA approval for targeted therapies on the horizon.
Dr. Khosroshahi emphasized the importance of raising awareness among medical professionals and the public. She advocated for incorporating IgG4-RD education into specialty training, publishing in high-impact journals, and fostering cross-disciplinary collaboration. Patient advocacy and validated educational resources also play crucial roles in increasing awareness and improving outcomes.
