Closing the Diagnostic, Monitoring Gap for IgG4-RD, With Robert Woodrick, MD

Diagnostic delays in immunoglobulin G4-related disease (IgG4-RD) still largely stem from underrecognition rather than a lack of tools, according to Robert S. Woodrick, MD, of Northwestern Medicine's Division of Rheumatology. Woodrick told RheumatologyLive that academic centers are seeing more referral awareness, but because IgG4-RD is a multisystem disorder that can progress slowly, patients often reach other specialties, including otolaryngology and gastroenterology, before rheumatology sees them. A 2025 review from the European Reference Network for Rare Connective Tissue Diseases identified 5 red flags, including organ swelling and pancreaticobiliary involvement, that reached full agreement among an expert task force, an effort intended to shorten that path to diagnosis in primary and secondary care.¹

Once a diagnosis is made, Woodrick said tracking subclinical disease progression remains difficult, since apparent clinical remission does not rule out ongoing fibrosis. He said certain baseline features, including very high serum IgG4 levels and multisystem involvement at diagnosis, can flag patients more likely to relapse, but serum IgG4 alone is an imperfect marker: many patients with active disease never have strikingly elevated levels, a limitation also raised in a systematic review of proposed IgG4-RD biomarkers, which found no single serologic or histologic marker with adequate diagnostic specificity.² In practice, Woodrick said monitoring depends on which organs are involved and how a patient has responded to treatment, with ultrasound used to follow salivary and parotid gland involvement and PET imaging reserved for detecting systemic inflammation that other modalities may miss, often in coordination with hepatology or pancreatic specialists for gastrointestinal disease.

That organ-by-organ complexity is also what drives Woodrick's approach to multidisciplinary care. He described a working consortium at Northwestern that includes otolaryngology, pathology, pulmonology, nephrology, ophthalmology, 2 gastroenterology subspecialists focused on pancreatic and liver disease, and 2 rheumatologists, meeting several times a year to review cases together. The group functions less as a formal referral pathway than a standing resource, Woodrick said, allowing specialists to consult each other when a diagnosis is unclear or when it is uncertain whether a treatment is working.

Woodrick was optimistic about where the field is headed, saying he expects the estimated incidence and prevalence of IgG4-RD to keep climbing as awareness spreads among subspecialists and referring physicians, not because the disease itself is becoming more common, but because more existing cases are being recognized. “I’m really optimistic about that. I think that’s happening,” he said.

References

1. Della-Torre E, Talarico R, Ballarin J, et al. Identification of red flags for IgG4-related disease: an international European Reference Network for Rare Connective Tissue Diseases framework. Lancet Rheumatol. 2025;7(1):e64-e71. https://doi.org/10.1016/S2665-9913(24)00192-9

2. Tang J, Cai S, Ye C, Dong L. Biomarkers in IgG4-related disease: a systematic review. Semin Arthritis Rheum. 2020;50(2):354-359. https://doi.org/10.1016/j.semarthrit.2019.06.018