Introduction: Immunoglobulin G4-related disease (IgG4-RD) is a systemic inflammatory disease characterized by elevated serum IgG4, tissue infiltration of IgG4-positive cells, and fibrosis. Although a number of IgG4-RD patients show sinonasal involvement, there is little known about sinonasal inflammation associated with IgG4-RD. This study aimed to describe the clinicopathological features of sinonasal inflammation associated with IgG4-RD and to compare with other inflammatory diseases, such as eosinophilic chronic rhinosinusitis (ECRS) and granulomatosis with polyangiitis (GPA). Methods: A retrospective analysis of clinicopathological features of patients with sinonasal lesions and high serum IgG4 was performed. Patient data were reviewed to determine whether they fulfilled the diagnostic criteria for other inflammatory diseases. Results: Six of 7 patients were diagnosed with IgG4-RD, while 1 patient was diagnosed with GPA. In the 6 patients with IgG4-RD, intranasal findings showed nasal polyps in 3 patients (50%) and nasal crusting in the 3 patients (50%). Computed tomography showed ethmoid sinus involvement in 5 patients (83%). Five of the 6 patients (83%) were diagnosed with IgG4-RD based on nasal biopsy, whereas 1 patient (17%) was diagnosed based on lacrimal gland biopsy. Four patients fulfilled the Japanese epidemiological survey of refractory ECRS (JESREC) criteria. However, none of the patients showed eosinophil infiltration. Although the patient with GPA showed high levels of serum IgG4 and tissue infiltration of IgG4-positive cells in the nasal biopsy, the patient showed common clinical features of GPA. Conclusion: Patients with sinonasal inflammation associated with IgG4-RD had similar clinical characteristics with ECRS and GPA. Histopathological findings of the nasal biopsy from clinically diagnosed GPA was consistent with that of IgG4-RD. Sinonasal inflammation associated with IgG4-RD should be diagnosed based not only on tissue infiltration of IgG4-positive cells but in conjunction with clinical findings such as local nasal characteristics, involvement of other organs, and serum antineutrophil cytoplasmic antibody levels. IgG4-RD should be ruled out in patients with eosinophilia without histopathological eosinophil infiltration.

Immunoglobulin G4-related disease (IgG4-RD) is a systemic inflammatory disease characterized by elevated serum IgG4 levels and tissue IgG4-positive cells. A part of IgG4-RD patients has sinonasal lesions. Because other inflammatory diseases also have features common to IgG4-RD, accurate knowledge of IgG4-RD is required. However, very little is known about IgG4-related rhinosinusitis. This study retrospectively analyzed clinicopathological features of IgG4-related rhinosinusitis and compared IgG4-related rhinosinusitis with other inflammatory diseases. Seven patients with sinonasal lesions and high serum IgG4 levels were retrospectively reviewed. Six of 7 patients were diagnosed with IgG4-RD, while one was diagnosed with granulomatosis with polyangiitis (GPA). In the 6 patients with IgG4-RD, intranasal findings showed nasal polyps in 3 patients (50%) and computed tomography showed ethmoid sinus involvement in 5 patients (83%), which shared common features with eosinophilic sinusitis (ECRS). However, no patients showed histopathological eosinophil infiltration. Although the patient with GPA revealed tissue infiltration of IgG4-positive cells in the nasal biopsy, the patient also had saddle nose and positivity of myeloperoxidase-antineutrophil cytoplasmic antibody (ANCA), which indicated GPA. We diagnosed the patient with GPA, which is a known mimicker of IgG4-RD. In this study, the patients with IgG4-related rhinosinusitis had clinical and pathological characteristics similar to those of ECRS and GPA. IgG4-related rhinosinusitis should be diagnosed based on not only tissue infiltration of IgG4-positive cells but also systemic findings including nasal findings and serum ANCA levels. IgG4-RD should be ruled out in patients with eosinophilia without histopathological eosinophil infiltration.

1.
Takano
K
,
Yamamoto
M
,
Takahashi
H
,
Himi
T
.
Recent advances in knowledge regarding the head and neck manifestations of IgG4-related disease
.
Auris Nasus Larynx
.
2017
;
44
(
1
):
7
17
.
2.
Erden
A
,
Bolek
EC
,
Yardimci
KG
,
Kilic
L
,
Bilgen
SA
,
Karadag
O
.
Do ANCA-associated vasculitides and IgG4-related disease really overlap or not
.
Int J Rheum Dis
.
2019
;
22
(
10
):
1926
32
.
3.
Oka
A
,
Ninomiya
T
,
Fujiwara
T
,
Takao
S
,
Sato
Y
,
Gion
Y
, et al
.
Serum IgG4 as a biomarker reflecting pathophysiology and post-operative recurrence in chronic rhinosinusitis
.
Allergol Int
.
2020
;
69
(
3
):
417
23
.
4.
Koyama
T
,
Kariya
S
,
Sato
Y
,
Gion
Y
,
Higaki
T
,
Haruna
T
, et al
.
Significance of IgG4-positive cells in severe eosinophilic chronic rhinosinusitis
.
Allergol Int
.
2019
;
68
(
2
):
216
24
.
5.
Umehara
H
,
Okazaki
K
,
Kawa
S
,
Takahashi
H
,
Goto
H
,
Matsui
S
, et al
.
The 2020 revised comprehensive diagnostic (RCD) criteria for IgG4-RD
.
Mod Rheumatol
.
2021
;
31
(
3
):
529
33
.
6.
Tokunaga
T
,
Sakashita
M
,
Haruna
T
,
Asaka
D
,
Takeno
S
,
Ikeda
H
, et al
.
Novel scoring system and algorithm for classifying chronic rhinosinusitis: the JESREC Study
.
Allergy
.
2015
;
70
(
8
):
995
1003
.
7.
Bloch
DA
,
Michel
BA
,
Hunder
GG
,
McShane
DJ
,
Arend
WP
,
Calabrese
LH
, et al
.
The American College of Rheumatology 1990 criteria for the classification of vasculitis. Patients and methods
.
Arthritis Rheum
.
1990
;
33
(
8
):
1068
73
.
8.
Ahmad
M
,
Spandorfer
R
,
Al Naqeeb
J
,
Khosroshahi
A
.
Mimickers of immunoglobulin G4-related disease
.
J Clin Rheumatol
.
2022
;
28
(
2
):
e647
50
.
9.
Wallace
ZS
,
Naden
RP
,
Chari
S
,
Choi
H
,
Della-Torre
E
,
Dicaire
JF
, et al
.
The 2019 American College of Rheumatology/European league against rheumatism classification criteria for IgG4-related disease
.
Arthritis Rheumatol
.
2020
;
72
(
1
):
7
19
.
10.
Satou
A
,
Notohara
K
,
Zen
Y
,
Nakamura
S
,
Yoshino
T
,
Okazaki
K
, et al
.
Clinicopathological differential diagnosis of IgG4-related disease: a historical overview and a proposal of the criteria for excluding mimickers of IgG4-related disease
.
Pathol Int
.
2020
;
70
(
7
):
391
402
.
11.
Strehl
JD
,
Hartmann
A
,
Agaimy
A
.
Numerous IgG4-positive plasma cells are ubiquitous in diverse localised non-specific chronic inflammatory conditions and need to be distinguished from IgG4-related systemic disorders
.
J Clin Pathol
.
2011
;
64
(
3
):
237
43
.
12.
Greco
A
,
Marinelli
C
,
Fusconi
M
,
Macri
GF
,
Gallo
A
,
De Virgilio
A
, et al
.
Clinic manifestations in granulomatosis with polyangiitis
.
Int J Immunopathol Pharmacol
.
2016
;
29
(
2
):
151
9
.
13.
Chang
SY
,
Keogh
KA
,
Lewis
JE
,
Ryu
JH
,
Cornell
LD
,
Garrity
JA
, et al
.
IgG4-positive plasma cells in granulomatosis with polyangiitis (Wegener's): a clinicopathologic and immunohistochemical study on 43 granulomatosis with polyangiitis and 20 control cases
.
Hum Pathol
.
2013
;
44
(
11
):
2432
7
.
14.
Fujieda
S
,
Imoto
Y
,
Kato
Y
,
Ninomiya
T
,
Tokunaga
T
,
Tsutsumiuchi
T
, et al
.
Eosinophilic chronic rhinosinusitis
.
Allergol Int
.
2019
;
68
(
4
):
403
12
.
15.
Zhou
L
,
Cao
F
,
Fan
S
,
Chen
P
,
Ding
S
,
Liu
G
, et al
.
A case of eosinophilic granulomatosis with polyangiitis complicated with a similar condition to IgG4 related lung disease
.
BMC Pulm Med
.
2019
;
19
(
1
):
154
.
16.
Della-Torre
E
,
Lanzillotta
M
,
Campochiaro
C
,
Bozzalla
E
,
Bozzolo
E
,
Bandiera
A
, et al
.
Antineutrophil cytoplasmic antibody positivity in IgG4-related disease: a case report and review of the literature
.
Medicine
.
2016
;
95
(
34
):
e4633
.
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