Table 3 Patients with the “Head and Neck-Limited” phenotype, who failed to fulfil the 2019 ACR/EULAR classification criteria

1

Two years prior to IgG4-RD diagnosis: diagnosis of MPA based on petechiae, glomerulonephritis (biopsy proven) and positive MPO-ANCA. Treated with RTX (1A and 1B), followed by AZA maintenance. At time of IgG4-RD diagnosis (under maintenance therapy with AZA monotherapy): left lacrimal gland enlargement. No other manifestations. Deemed to be coexisting MPA and IgG4-RD, with the latter accounting for the dacryoadenitis. The rational was (i) the other vasculitic manifestations were well controlled; and (ii) the previous reports of coexistence of AAV and IgG4-RD. However, we acknowledge the diagnostic uncertainty

Lacrimal gland: LPC infiltrate and storiform fibrosis. > 50 IgG4 + PC/hpf with IgG4/IgG ratio > 0.40

0.81

Probable IgG4-RD

Fulfils entry criterion. Fulfils exclusion criterion (MPO-ANCA)

Weighted score = 27

• Histology = 13

• IHC = 14

2

Sinusitis, cough and low-grade fever. Destructive process in sphenoid sinus, lymphadenopathy and lung changes (ground glass opacities and small nodules). ANCA negative. Biopsy without evidence of AAV or malignancy

Sphenoid sinus: LPC infiltrate and fibrosis (without storiform appearance). Abundant IgG4 + PC/hpf (unable to quantitate), with IgG4/IgG ratio > 0.40

3.43

Definite IgG4-RD

Fulfils entry criterion. Fulfils exclusion criterion (fever)

Weighted score = 22

• Histology = 4

• IHC = 14

• s-IgG4 = 4

3

Inflammatory mass in nasal septum. No other definite manifestations (albeit possible idiopathic pancreatitis 10 years prior). ANCA negative. Biopsy without evidence of AAV or malignancy

Nasal septum: LPC infiltrate and fibrosis (without storiform appearance). Abundant IgG4 + PC/hpf (unable to quantitate), with IgG4/IgG ratio > 0,3

2.08

Definite IgG4-RD

Does not fulfil entry criterion (nasal septum not a typical organ). No exclusion criteria

Weighted score = 15

• Histology = 4

• IHC = 7

• s-IgG4 = 4

4

Chronic rhinosinusitis and arthralgia. Negative ANCA. FDG-uptake in tonsils, oropharynx, and bilateral parotid and submandibular glands. No other manifestations. Positive anti-RNP, but no arthritis or other manifestations suggestive of MCTD or other connective tissue disease

Waldeyers ring: LPC infiltrate. 88 IgG4 + PC/hpf, with IgG4/IgG ratio > 0.4

4.30

Definite IgG4-RD

Fulfils entry criterion. Fulfils exclusion criterion (anti-RNP)

Weighted score = 38

• Histology = 4

• IHC = 14

• s-IgG4 = 6

• Two sets of glands = 14

5

Right lacrimal gland enlargement. FDG-uptake in bilateral parotid and submandibular glands. No other manifestations. Positive MPO-ANCA, but no other manifestations consistent with AAV. As there was no evidence of vasculitis or extraglandular vasculitic manifestations, we believe that the presentation was more consistent with IgG4-RD than AAV

Lacrimal gland: LPC infiltrate. > 100 IgG4 + PC/hpf, with IgG4/IgG ratio > 0.4

2.30

Definite IgG4-RD

Fulfils entry criterion. Fulfils exclusion criterion (MPO-ANCA)

Weighted score = 36

• Histology = 4

• IHC = 14

• s-IgG4 = 4

• Two sets of glands = 14

6

Lacrimal gland enlargement. FDG-uptake in bilateral parotid glands. No other manifestations

Lacrimal glands: inconclusive

3.17

Possible IgG4-RD

Fulfils entry criterion. No exclusion criteria

Weighted score = 18

• s-IgG4 = 4

• Two sets of glands = 14

7

Orbital pseudotumor and ipsilateral lacrimal gland enlargement. FDG uptake in bilateral lacrimal and submandibular glands. No other manifestations. Positive MPO-ANCA and microscopic hematuria, with renal biopsy consistent with low-grade AAV (without evidence of IgG4-related kidney disease). Considered to be coexisting MPA and IgG4-RD, with the latter accounting for the head and neck manifestations. However, we acknowledge the diagnostic uncertainty

Lacrimal glands: LPC infiltrate and fibrosis (without storiform appearance). > 90 IgG4 + PC/hpf, unable to estimate ratio

1.30

Probable IgG4-RD

Fulfils entry criterion. Fulfils exclusion criterion (MPO-ANCA)

Weighted score = 25

• Infiltrate = 4

• IHC = 7

• Two sets of glands = 14

8

Right submandibular gland enlargement and lymphadenopathy. FDG-uptake in right parotid and submandibular glands. No other manifestations

Lymph node: LPC infiltrate. > 100 IgG4 + PC/hpf and IgG4/IgG ratio 0.80

6.70

Possible IgG4-RD (lymph node biopsy not considered)

Fulfils entry criterion. No exclusion criteria

Weighted score = 10

• Histology = 4

• s-IgG4 = 6

(lymph node biopsy not used for IHC scoring)

9

Pharyngeal fullness and low-grade fever. FDG uptake in oropharynx and lymph nodes. No other manifestations

Waldeyers ring: LPC infiltrate and fibrosis (without storiform appearance). Abundant IgG4 + PC/hpf (uanable to quantify), with IgG4/IgG ratio > 0.50

3.40

Definite IgG4-RD

Does not fulfil entry criterion (oropharynx not a typical organ). Fulfils exclusion criterion (fever)

Weighed score = 22

• Histology = 4

• IHC = 14

• s-IgG4 = 4