2019 ACR/EULAR Classification Criteria for IgG4-Related Disease

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The American College of Rheumatology and the European League Against Rheumatism developed and validated an international set of classification criteria for IgG4-related disease.

The American College of Rheumatology and the European League Against Rheumatism have developed and validated classification criteria for immunoglobulin G4-related disease (IgG4-RD). The new criteria have been published in the Annals of the Rheumatic Diseases.

According to the researchers, the classification of IgG4-RD requires correlating clinical, serologic, radiologic, and pathologic data; however, none of these approaches alone provide definitive evidence for accurate disease classification in patients.

The objective of this study was to develop and validate an international set of classification criteria for IgG4-RD using data from all 4 domains of evidence.

Entry Criteria

Entry criteria for IgG4-RD were defined as (1) clinical or radiologic involvement of at least 1 of 11 possible organs, including the pancreas, bile ducts, orbits, lacrimal glands, major salivary glands, retroperitoneum, kidney, lung, aorta, pachymeninges, or thyroid gland. Involvement can be defined as enlargement of the organ or presence of a tumor-like mass within the affected organ, also including 3 organ-specific features with reference to the bile ducts, aorta, and lungs; (2) pathologic evidence of an inflammatory process accompanied by a lymphoplasmacytic infiltrate of uncertain etiology in 1 of these same organs.

Exclusion Criteria

Exclusion criteria for the classification of a potential IgG4-RD case includes a total of 32 clinical, serologic, radiologic, and pathologic items. The presence of any of these items eliminates the patient from IgG4-RD classification; however, the exclusion criteria should not be viewed as a checklist, but rather serve as a reminder of evaluations that may be appropriate to consider in specific clinical scenarios.

Clinical Exclusion Criteria

• Fever

• No objective response to glucocorticoids

Serologic Exclusion Criteria

• Leukopenia and thrombocytopenia with no alternate explanation

• Peripheral eosinophilia

• Positive antineutrophil cytoplasmic antibody, specifically against proteinase 3 or myeloperoxidase

• Positive Sjögren syndrome-related antigen A/Ro or Sjögren syndrome-related antigen B/La antibody

• Positive double-stranded DNA, ribonucleoprotein, or Smith antibody

• Other disease-specific autoantibody

• Cryoglobulinemia

Radiologic Exclusion Criteria

• Known radiologic findings suspicious for malignancy or infection that have not been sufficiently investigated, including rapid radiologic progression, long bone abnormalities consistent with Erdheim-Chester disease, and splenomegaly

Pathologic Exclusion Criteria

• Cellular infiltrates suggesting malignancy that has not been sufficiently evaluated

• Markers consistent with inflammatory myofibroblastic tumor

• Prominent neutrophilic inflammation, including necrotizing vasculitis, prominent necrosis, primarily granulomatous inflammation, and pathologic features of macrophage/histiocytic disorder

• Hashimoto thyroiditis (if only the thyroid is affected)

• Known diagnosis of multicentric Castleman disease, and Crohn disease or ulcerative colitis (if only pancreatobiliary disease is present)

Inclusion Criteria

Classification of IgG4-RD must include the application of 8 weighted inclusion criteria domains that address clinical findings, serologic results, radiologic assessments, and pathologic interpretations. Within each criteria domain, items were arranged according to the degree to which they either increased or decreased the likelihood of classification. Each potential criterion was ranked on a Likert scale from -5 (highly confident the patient does not have IgG4-RD if the item is present) to +5 (highly confident the patient has IgG4-RD if the item is present). Items with average confidence between -2 and +2 must be excluded from further consideration.


• Uninformative biopsy (0)

• Dense lymphocytic infiltrate (+4)

• Dense lymphocytic infiltrate and obliterative phlebitis (+6)

• Dense lymphocytic infiltrate and storiform fibrosis with or without obliterative phlebitis (+13)

• Immunostaining (0-16)

Serum IgG4 concentration

• Normal or not checked (0)

• Higher than normal but <2× the upper limit of normal (ULN; +4)

• 2× to 5× ULN (+6)

• ≥5× ULN (+11)

Bilateral lacrimal, parotid, sublingual, and submandibular glands

• No set of glands involved (0)

• 1 set of glands involved (+6)

• ≥2 sets of glands involved (+14)

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• Not checked or neither of the items listed is present (0)

• Peribronchovascular and septal thickening (+4)

• Paravertebral band-like soft tissue in the thorax (+10)

Pancreas and biliary tree

• Not checked or none of the items listed is present (0)

• Diffuse pancreas enlargement (loss of lobulations; +8)

• Diffuse pancreas enlargement and capsule-like rim with decreased enhancement (+11)

• Pancreas (either of above) and biliary tree involvement (+19)


• Not checked or none of the items listed is present (0)

• Hypocomplementemia (+6)

• Renal pelvis thickening/soft tissue (+8)

• Bilateral renal cortex low-density areas (+10)


• Not checked or neither of the items listed is present (0)

• Diffuse thickening of the abdominal aortic wall (+4)

• Circumferential or anterolateral soft tissue around the infrarenal aorta or iliac arteries (+8)


The IgG4-RD classification criteria is fulfilled if entry criteria are met, no exclusion criteria are present, and the total points add up to ≥20.

According to the researchers, the new criteria for IgG4-RD are not intended for use in clinical practice to diagnose the disease. When a patient is clinically diagnosed with IgG4-RD, failure to fulfill all classification criteria should not prevent disease management; however, the criteria may provide a useful framework for physicians considering an IgG4-RD diagnosis in a patient and highlight findings that increase the likelihood that a patient has IgG4-RD. In addition, the exclusion criteria should not be interpreted as a list of studies or tests physicians must conduct on every patient.


Wallace ZS, Naden RP, Chari S, et al. The 2019 American College of Rheumatology/European League against rheumatism classification criteria for IgG4-related disease. Ann Rheum Dis. 2020;79(1):77-87.