Research Summary

Leading Organizations Develop Classification Criteria for IgG4‐Related Disease

A multispecialty group assembled by the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR) has developed and validated the first international set of classification criteria for IgG4‐related disease (IgG4‐RD). The classification criteria can help facilitate the identification of people with IgG4-RD for inclusion in clinical trials and observational studies.

“The 2019 ACR/EULAR IgG4‐RD criteria represent a significant milestone in IgG4‐RD,” the criteria authors wrote.

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IgG4‐RD is now recognized as a distinct condition. Because of this, combined with the condition’s multiorgan nature and the absence of a single diagnostic feature, classification criteria are needed to conduct high‐quality clinical and epidemiologic investigations of the disease.

“The 2019 IgG4‐RD classification criteria are one of the first sets of classification criteria in rheumatology to include absolute exclusion criteria that are not based solely on having an alternative diagnosis, but rather focus on clinical, serologic, radiologic, and pathologic features,” the authors wrote. 

To create the criteria, ACR and EULAR selected 86 physicians to form an international multispecialty group. The group members identified, weighted, and tested potential classification criteria via consensus exercises, existing literature, derivation and validation cohorts, and multicriterion decision analysis.

The group defined entry criteria as characteristic clinical or radiologic involvement of a typical organ or pathologic evidence of an inflammatory process accompanied by a lymphoplasmacytic infiltrate of uncertain etiology in one of those same organs.

Among the inclusion criteria were the following:

  • Peribronchovascular and septal thickening in the lung must be determined by a cross‐sectional imaging study of the chest.
  • The type of biliary involvement that is highly consistent with IgG4‐related sclerosing cholangitis involves the proximal biliary tract. The bile duct walls often have smooth thickening.
  • Renal pelvic wall thickening can be either unilateral or bilateral, usually without severe stenosis or luminal irregularity.

Among the exclusion criteria were the following clinical, serologic, radiologic, and pathologic features:

  • No objective response to glucocorticoids
  • Positive antineutrophil cytoplasmic antibody test results
  • Long bone abnormalities consistent with Erdheim‐Chester disease
  • Markers consistent with inflammatory myofibroblastic tumor
  • Crohn disease (if pancreatobiliary disease is present)

Based on the criteria, the multispecialty group developed the following 3-step classification process:

  1. Demonstrate that a potential IgG4‐RD case has involvement of at least 1 of 11 possible organs in a manner consistent with IgG4‐RD.
  2. Apply the exclusion criteria, which comprise 32 clinical, serologic, radiologic, and pathologic items. If a patient meets any of the criteria, he or she is eliminated from IgG4‐RD classification.
  3. Apply the 8 weighted inclusion criteria domains, addressing clinical findings, serologic results, radiology assessments, and pathology interpretations.

The first validation cohort demonstrated a specificity of 99.2% and sensitivity of 85.5% at a 20-point threshold. The second validation cohort demonstrated a specificity of 97.8% and sensitivity of 82.0% at a 20-point threshold. According to the authors, the criteria were shown to have robust test characteristics over a wide range of thresholds.

“Our approach reflects the fact that in clinical practice, information from clinical, serologic, radiologic, and pathologic evaluations must be integrated to arrive at a confident decision about whether to classify a patient as having IgG4‐RD,” the authors wrote.

—Colleen Murphy

Reference:

Wallace ZS, Naden RP, Chari S, et al; The American College of Rheumatology/European League Against Rheumatism IgG4-Related Disease Classification Criteria Working Group. The 2019 American College of Rheumatology/European League Against Rheumatism classification criteria for IgG4‐related disease [published online December 2, 2019]. Arthritis Rheumatol. doi:10.1002/art.41120.