Proposal for a new clinical entity, IgG4-positive multiorgan lymphoproliferative syndrome: analysis of 64 cases of IgG4-related disorders.
BACKGROUND
Mikulicz's disease (MD) has been considered as one manifestation of Sjögren's syndrome (SS). Recently, it has also been considered as an IgG(4)-related disorder.


OBJECTIVE
To determine the differences between IgG(4)-related disorders including MD and SS.


METHODS
A study was undertaken to investigate patients with MD and IgG(4)-related disorders registered in Japan and to set up provisional criteria for the new clinical entity IgG(4)-positive multiorgan lymphoproliferative syndrome (IgG(4)+MOLPS). The preliminary diagnostic criteria include raised serum levels of IgG(4) (>135 mg/dl) and infiltration of IgG(4)(+) plasma cells in the tissue (IgG(4)+/IgG+ plasma cells >50%) with fibrosis or sclerosis. The clinical features, laboratory data and pathologies of 64 patients with IgG(4)+MOLPS and 31 patients with typical SS were compared.


RESULTS
The incidence of xerostomia, xerophthalmia and arthralgia, rheumatoid factor and antinuclear, antiSS-A/Ro and antiSS-B/La antibodies was significantly lower in patients with IgG(4)+MOLPS than in those with typical SS. Allergic rhinitis and autoimmune pancreatitis were significantly more frequent and total IgG, IgG(2), IgG(4) and IgE levels were significantly increased in IgG(4)+MOLPS. Histological specimens from patients with IgG(4)+MOLPS revealed marked IgG(4)+ plasma cell infiltration. Many patients with IgG(4)+MOLPS had lymphocytic follicle formation, but lymphoepithelial lesions were rare. Few IgG(4)+ cells were seen in the tissue of patients with typical SS. Thirty-eight patients with IgG(4)+MOLPS treated with glucocorticoids showed marked clinical improvement.


CONCLUSIONS
Despite similarities in the involved organs, there are considerable clinical and pathological differences between IgG(4)+MOLPS and SS. Based on the clinical features and good response to glucocorticoids, we propose a new clinical entity: IgG(4)+MOLPS.
Masaki
Y
Y
Department of Hematology and Immunology, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Kahoku-gun, Ishikawa, 920-0293, Japan. yasum@kanazawa-med.ac.jp
Dong
L
L
Kurose
N
N
Kitagawa
K
K
Morikawa
Y
Y
Yamamoto
M
M
Takahashi
H
H
Shinomura
Y
Y
Imai
K
K
Saeki
T
T
Azumi
A
A
Nakada
S
S
Sugiyama
E
E
Matsui
S
S
Origuchi
T
T
Nishiyama
S
S
Nishimori
I
I
Nojima
T
T
Yamada
K
K
Kawano
M
M
Zen
Y
Y
Kaneko
M
M
Miyazaki
K
K
Tsubota
K
K
Eguchi
K
K
Tomoda
K
K
Sawaki
T
T
Kawanami
T
T
Tanaka
M
M
Fukushima
T
T
Sugai
S
S
Umehara
H
H
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D003937:Diagnosis, Differential; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis*; D007765:Lacrimal Apparatus / Q000473:pathology; D008232:Lymphoproliferative Disorders / Q000175:diagnosis / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D008882:Mikulicz' Disease / Q000175:diagnosis / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D011239:Prednisolone / Q000627:therapeutic use; D012189:Retrospective Studies; D012470:Salivary Glands, Minor / Q000473:pathology; D012859:Sjogren's Syndrome / Q000175:diagnosis / Q000276:immunology / Q000473:pathology; D013577:Syndrome; D055815:Young Adult
D005938:Glucocorticoids; D007074:Immunoglobulin G; D011239:Prednisolone