Table 1

Exclusion criteria definitions

 Fever: Documented, recurrent temperature>38°C, with fever being a prominent part of the patient’s overall presentation with the underlying disease, in the absence of any clinical features of infection.
 No objective response to glucocorticoids: If the patient has been treated with prednisone at a minimum of 40 mg/day (~0.6 mg/kg/day) for a period of 4 weeks, the patient has not demonstrated an objective clinical response. An objective response includes unequivocal improvement of the clinical lesions, biochemical abnormalities, or radiological findings. There are two two additional points to consider with regard to glucocorticoid response: Improvement only in the serum IgG4 concentration should not be regarded as a clinical response without improvement in other aspects of the disease. Some forms of IgG4-related disease (IgG4-RD) associated with advanced fibrosis, for example, some cases of retroperitoneal fibrosis or sclerosing mesenteritis, may not demonstrate obvious radiological responses to glucocorticoids.
 Leucopenia and thrombocytopenia without alternative explanation: Reduction in the total white cell count and platelet count to levels below those normal for the reference laboratory, having no apparent explanation except for the underlying disease. Reductions in both the white cell count and platelet count are unusual in IgG4-RD but are typical of, for example, myelodysplastic syndromes, haematopoietic malignancies, and autoimmune conditions within the systemic lupus erythematosus spectrum.
 Peripheral eosinophilia: To a concentration of>3000 mm3.
 Positive antineutrophil cytoplasmic antibody (ANCA): ELISA results positive for ANCA targeted against proteinase three or myeloperoxidase.
 Positive antibodies: Ro, La, double-stranded DNA, RNP, or Sm antibodies positive in titrers greater than normal suggest an alternative diagnosis. Other autoantibody associated with high specificity for another immune-mediated condition is a reasonable explanation for the patient’s presentation. Such specific autoantibodies include antisynthetase antibodies (eg, anti-Jo-1), anti-topoisomerase III (Scl-70), and anti-phospholipase A2 receptor antibodies. This does not include autoantibodies of low specificity, such as rheumatoid factor, antinuclear antibodies, antimitochondrial antibodies, anti-smooth muscle antibodies, and antiphospholipid antibodies.
 Cryoglobulinemia: Cryoglobulinemia (type I, II, or III) occurring in a clinical context that provides a reasonable explanation for the patient’s presentation.
 Known radiological findings suspicious for malignancy or infection that have not been investigated sufficiently: Such radiological findings include mass lesions that have not been evaluated thoroughly, necrosis, cavitation, hypervascular or exophytic mass, bulky or matted lymphadenopathy, loculated abdominopelvic fluid collection, among others.
 Rapid radiological progression: Defined as significant worsening within a 4–6 week interval.
 Long bone abnormalities consistent with Erdheim-Chester disease: Multifocal osteosclerotic lesions of the long bones, usually associated with bilateral diaphyseal involvement.
 Splenomegaly:>14 cm in the absence of alternative explanation (eg, portal hypertension).
 Cellular infiltrates suspicious for malignancy that have not been investigated sufficiently: A high likelihood of malignancy may be suggested by cellular atypia, a monotypic nature of immunohistochemistry findings, or light chain restriction on in situ hybridizsation studies. If malignancy is suspected, this must be excluded by appropriate studies before inclusion.
 Markers consistent with inflammatory myofibroblastic tumour: Known positivity for a marker suggestive of inflammatory myofibroblastic tumour, for example, anaplastic lymphoma kinase one or ROS, a receptor tyrosine kinase that is encoded by the gene ROS1
 Prominent neutrophilic inflammation: Neutrophilic infiltrates are unusual in IgG4-RD, with the exception of occasional examples in the lung or near mucosal sites. Extensive neutrophilic infiltrates or neutrophilic abscesses strongly indicate the possibility of a non- IgG4-RD diagnosis.
 Necrotising vasculitis: Although vascular injury (eg, obliterative phlebitis or arteritis) is a hallmark of IgG4-RD, the presence of fibrinoid necrosis within blood vessel walls provides strong evidence against IgG4-RD.
 Prominent necrosis: Small foci of necrosis may rarely be present around the luminal surface of ductal organs, but zonal necrosis with no alternative explanation (eg, stenting) provides strong evidence against IgG4-RD.
 Primary granulomatous inflammation: Inflammation rich in epithelioid histiocytes, including multinucleated giant cell formation and granuloma formation, is highly atypical of IgG4- RD
 Pathological features of a macrophage/histiocytic disorder: For example: known S100-positive macrophages demonstrating emperipolesis, a pathological feature of Rosai-Dorfman disease.
Specific disease exclusions
 Known diagnoses of the following diseases are exclusion criteria: Multicentric Castleman’s disease, Crohn’s disease (if pancreatobiliary disease is present), ulcerative colitis (if pancreatobiliary disease is present), Hashimoto thyroiditis (if the thyroid is the only proposed disease manifestation).: Patients with IgG4-RD can certainly have Hashimoto thyroiditis separately from IgG4-RD, but Hashimoto thyroiditis is part of the IgG4-RD spectrum.