The 2020 revised comprehensive diagnostic (RCD) criteria for IgG4-RD

Figures & data

Table 1. Revised comprehensive diagnostic criteria for IgG4-RD working group, the research program for intractable disease by the ministry of health, labor and welfare (MHLW) Japan.

Kazuichi Okazaki (Chairman)	Gastroenterology	Kansai Medical University
Hisanori Umehara (Leader)	Rheumatology	Nagahama City Hospital
Shigeyuki Kawa	Gastroenterology	Matsumoto Dental University
Hiroki Takahashi	Rheumatology	Sapporo Medical University
Hiroshi Goto	Ophthalmology	Tokyo Medical University
Shoko Matsui	Respirology	University of Toyama
Nobukazu Ishizaka	Cardiology	Oosaka Medical College
Takashi Akamizu	Endocrinology	Wakayama Medical University
Yasuharu Sato	Pathology	Okayama University
Mitsuhiro Kawano	Rheumatology and Nephrology	Kanazawa University

Table 2. The 2020 Revised comprehensive diagnostic (RCD) criteria for IgG4-RD.

[Item 1] clinical and radiological features

One or more organs show diffuse or localized swelling or a mass or nodule characteristic of IgG4-RD. In single organ involvement, lymph node swelling is omitted.

[Item 2] serological diagnosis

Serum IgG4 levels greater than 135 mg/dl.

[Item 3] pathological diagnosis

Positivity for two of the following three criteria:

① Dense lymphocyte and plasma cell infiltration with fibrosis.

② Ratio of IgG4-positive plasma cells /IgG-positive cells greater than 40% and the number of IgG4-positive plasma cells greater than 10 per high powered field

③Typical tissue fibrosis, particularly storiform fibrosis, or obliterative phlebitis

Diagnosis:

Definite: 1) +2) +3)

Probable: 1) +3):

Possible: 1) +2)

Explanatory note 1: Combination of organ-specific diagnostic criteria*.

Patients with a possible or probable diagnosis by comprehensive diagnostic criteria who fulfill the organ-specific criteria for IgG4-RD are regarded as being definite for IgG4-RD.

*Diagnostic criteria according to the IgG4-related organ:.

① International consensus diagnostic criteria for autoimmune pancreatitis⁷⁾, ② IgG4-related lacrimal gland, saliva adenitis diagnostic criteria⁸⁾, ③ Diagnostic criteria for IgG4-related kidney disease⁹⁾, ④ Clinical diagnostic criteria of IgG4-related sclerosing cholangitis 2012¹⁰⁾, ⑤Diagnostic criteria for IgG4-related ophthalmic disease¹¹⁾, ⑥Diagnostic criteria for IgG4-related respiratory disease¹²⁾, ⑦ Diagnostic criteria for IgG4-related large periarteritis/periarteritis and retroperitoneal fibrosis¹³⁾.

Explanatory note 2: exclusion diagnosis.

1) It is important to acquire tissue samples from each involved organ to distinguish malignant tumors (e.g. cancer, malignant lymphoma) and similar benign conditions (e.g. Sjögren syndrome, primary sclerosing cholangitis, multicentric Castleman’s disease, secondary retroperitoneal fibrosis, granulomatosis with polyangiitis, sarcoidosis, eosinophilic granulomatosis with polyangiitis).

2) It is important to exclude an infectious- or inflammation-related disease in patients with high fever, highly elevated CRP and neutrophilia.

Explanatory note 3: pathologic diagnosis.

1) The numbers of IgG4-positive cells are usually more abundant in resected organs and partially enucleated tissue than in tissue samples obtained by needle biopsy or endoscopic biopsy. Thus, it is important to not be too particular about cell number and to provide a precise judgment.

2) Storiform fibrosis is defined as spindle-shaped cells, inflammatory cells and fine collagen fibers forming a flowing arrangement. Obliterative phlebitis is defined as fibrous venous obliteration with inflammatory cells. Both are helpful for a diagnosis of IgG4-RD. ① and ③ without ② can only be applied in a case with poor IgG4 and/or IgG staining.

Explanatory note 4: steroid reactivity.

Steroid trial is not recommended. However, if patients do not respond to initial steroid therapy, the diagnosis should be reconsidered.

Figure 1. Storiform fibrosis and obliterative phlebitis. (a) Storiform fibrosis: spindle‐shaped cells, inflammatory cells and fine collagen fibers are forming a flowing arrangement. The infiltration of plasma cells is easy to recognize. Eosinophils are also intermingled (hematoxylin and eosin stain). (b) Obliterative phlebitis: fibrous venous obliteration with inflammatory cells (arrows). L:lumen.