The 2019 American College of Rheumatology/European League Against Rheumatism classification criteria for IgG4-RD
| Step | Categorical assessment or numerical weight |
| Step 1. Entry criteria | |
| Characteristic* clinical or radiological involvement of a typical organ (eg, pancreas, salivary glands, bile ducts, orbits, kidney, lung, aorta, retroperitoneum, pachymeninges or thyroid gland (Riedel’s thyroiditis)) OR pathological evidence of an inflammatory process accompanied by a lymphoplasmacytic infiltrate of uncertain aetiology in one of these same organs | Yes† or No |
| Step 2. Exclusion criteria: domains and items‡ | Yes or No§ |
| Clinical | |
| Fever | |
| No objective response to glucocorticoids | |
| Serological | |
| Leucopenia and thrombocytopenia with no explanation | |
| Peripheral eosinophilia | |
| Positive antineutrophil cytoplasmic antibody (specifically against proteinase 3 or myeloperoxidase) | |
| Positive SSA/Ro or SSB/La antibody | |
| Positive double-stranded DNA, RNP or Sm antibody | |
| Other disease-specific autoantibody | |
| Cryoglobulinemia | |
| Radiological | |
| Known radiological findings suspicious for malignancy or infection that have not been sufficiently investigated | |
| Rapid radiological progression | |
| Long bone abnormalities consistent with Erdheim-Chester disease | |
| Splenomegaly | |
| Pathological | |
| Cellular infiltrates suggesting malignancy that have not been sufficiently evaluated | |
| Markers consistent with inflammatory myofibroblastic tumour | |
| Prominent neutrophilic inflammation | |
| Necrotizing vasculitis | |
| Prominent necrosis | |
| Primarily granulomatous inflammation | |
| Pathologic features of macrophage/histiocytic disorder | |
| Known diagnosis of the following: | |
| Multicentric Castleman’s disease | |
| Crohn’s disease or ulcerative colitis (if only pancreatobiliary disease is present) | |
| Hashimoto thyroiditis (if only the thyroid is affected) | |
|
If case meets entry criteria and does not meet any exclusion criteria,
proceed to step 3. | |
| Step 3. Inclusion criteria: domains and items ¶ | |
| Histopathology | |
| 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, as follows: |
| Assigned weight is 0 if the IgG4+:IgG+ ratio is 0%–40% or indeterminate and the number of IgG4+ cells/hpf is 0–9.‡‡ Assigned weight is 7 if: (1) the IgG4+:IgG+ ratio is ≥41% and the number of IgG4+cells/hpf is 0–9 or indeterminate or (2) the IgG4+:IgG+ ratio is 0–40% or indeterminate and the number of IgG4+ cells/hpf is ≥10 or indeterminate. Assigned weight is 14 if: (1) the IgG4+:IgG+ ratio is 41%–70% and the number of IgG4+ cells/hpf is ≥10 or (2) the IgG4+:IgG+ ratio is ≥71% and the number of IgG4+ cells/hpf is 10–50. Assigned weight is 16 if the IgG4+:IgG+ ratio is ≥71% and the number of IgG4+ cells/hpf is ≥51. | |
| Serum IgG4 concentration | |
| Normal or not checked | 0 |
| >Normal but <2× upper limit of normal | +4 |
| 2–5× upper limit of normal | +6 |
| ≥>5× upper limit of normal | +11 |
| Bilateral lacrimal, parotid, sublingual and submandibular glands | |
| No set of glands involved | 0 |
| One set of glands involved | +6 |
| Two or more sets of glands involved | +14 |
| Chest | |
| 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 |
| Kidney | |
| 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 |
| Retroperitoneum | |
| 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 |
| Step 4: Total inclusion points | |
| A case meets the classification criteria for IgG4-RD if the entry criteria are met, no exclusion criteria are present, and the total points is ≥20 |
*Refers to enlargement or tumour-like mass in an affected organ except in (1) the bile ducts, where narrowing tends to occur, (2) the aorta, where wall thickening or aneurysmal dilatation is typical and (3) the lungs, where thickening of the bronchovascular bundles is common.
†If entry criteria are not fulfilled, the patient cannot be further considered for classification as having IgG4-RD.
‡Assessment for the presence of exclusion criteria should be individualised depending on a patient’s clinical scenario.
§If exclusion criteria are met, the patient cannot be further considered for classification as having IgG4-RD.
¶Only the highest weighted item in each domain is scored.
**Biopsies from lymph nodes, mucosal surfaces of the gastrointestinal tract and skin are not acceptable for use in weighting the immunostaining domain.
††‘Indeterminate’ refers to a situation in which the pathologist is unable to clearly quantify the number of positively staining cells within an infiltrate, yet can still ascertain that the number of cells is at least 10/hpf. For a number of reasons, most often pertaining to the quality of the immunostain, pathologists are sometimes unable to count the number of IgG4+ plasma cells with precision yet even so, can be confident in grouping cases into the appropriate immunostaining result category.
hpf, high-power field; IgG4-RD, IgG4-related disease.