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Journal of Peking University (Health Sciences) ›› 2021, Vol. 53 ›› Issue (6): 1043-1048. doi: 10.19723/j.issn.1671-167X.2021.06.006

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Clinical characteristics of central nervous system involvement in IgG4 related diseases

MENG Guang-yan1,2,ZHANG Yun-xiao1,3,ZHANG Yu-xin1,LIU Yan-ying1,4,△   

  1. 1. Department of Rheumatology and Immunology, Peking University People’s Hospital, Beijing 100044, China
    2. Department of Clinical Laboratory, Peking University People’s Hospital, Beijing 100044, China
    3. Department of Internal Medicine, Hospital of Qinghe Branch of Beijing Prison Administration, Tianjin 300481, China
    4. Department of Rheumatology and Immunology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China
  • Received:2021-08-19 Online:2021-12-18 Published:2021-12-13
  • Contact: Yan-ying LIU
  • Supported by:
    National Natural Science Foundation of China(81971520)

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Abstract:

Objective: To improve the understanding of the clinical characteristics of immunoglobulin G4-related disease (IgG4-RD) with central nervous system (CNS) involvement, so as to contribute to the early diagnosis and treatment. Methods: In this study, 10 patients with IgG4-RD with CNS involvement were selected. Clinical data including demographic features, clinical manifestations, organ involvement, laboratory findings, radiological results, pathology, treatments and outcomes were collected retrospectively. Results: Among the 10 IgG4-RD patients complicated with CNS involvement, 6 cases manifested as pituitary involvement and 4 cases manifested as dural involvement. Only 2 patients had nervous system involvement alone, while the left patients were complicated with other organ involvement besides nervous system. Half of the patients presented nervous system involvement as the initial manifestation, and the main symptoms of nervous system included polydipsia, polyuria, headache, decreased vision and so on. In the laboratory examination, the serum IgG4 level was increased in 9 cases (90.0%), and the total serum IgE was increased in 7 cases (87.5%). At the same time, their IgG, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were increased, while complement (C) 3 and C4 were decreased in some patients. Eight patients underwent tissue biopsies in different parts, the pathological examination showed a large number of lymphocyte and plasma cell infiltration, accompanied by fibrous tissue proliferation in part. All the patients were treated with glucocorticoids, and 8 cases (80%) were given immunosuppressants at the same time, and 3 cases were treated with rituximab when they expe-rienced disease relapse. As a result, 2 cases (20%) achieved complete remission (CR), and 8 cases (80%) achieved partial remission (PR). The median follow-up time was 13.5 months, and 4 cases relapsed. Conclusion: Pituitary and dura are common affected organs of IgG4-RD with CNS involvement. Most IgG4-RD patients with CNS involvement are combined with other organ involvement, but half of them presented nervous system involvement as the initial manifestation, and the symptoms are not typical. In order to make an early diagnosis, laboratory, imaging examination and tissue biopsy should be taken into consideration in combination if necessary.

Key words: Immunoglobulin G4-related diseases, Central nervous system, Diagnosis, differential, Hypophysitis, Meningitis

CLC Number: 

  • R593.2

Table 1

Clinical characteristics of 10 IgG4-RD patients"

Case Gender Onset age/
years		 Disease
course/years		 Symptom Extra-CNS involvement
Initial symptoms Accompanying symptoms
1 M 53 8.0 Xerophthalmia Thirsty, polydipsia, polyuria,
submandibular masses		 LG, SMG
2 M 58 2.0 Abdominal pain and distension Diarrhea Pancreas
3 M 56 1.0 Epigastric pain Shortness of breath, polydipsia and polyuria Pancreas, lung, pleura,
LN, PG, SMG, BD
4 F 44 12.0 Eyelid swelling Polydipsia, polyuria and shortness of breath Pancreas, lung, kidney,
LG, SMG, PG
5 M 40 23.0 Polydipsia, polyuria Weight loss, lumbago pain Pancreas, kidney, ureter, LN
6 M 43 7.0 Thirsty, polydipsia, polyuria Eyelid swelling LG, LN
7 M 52 7.0 Headache Left facial atrophy Lung
8 M 15 1.0 Eyes pain Headache, vision and hearing loss No
9 M 52 2.5 Eyelid swelling Epilepsy, eye pain, vision loss,
buccal and submandibular swelling		 LG, SMG, PG
10 M 46 1.0 Right ear pain Headache, hoarseness,
muscular atrophy of lower limbs		 No

Table 2

Laboratory examination results of 10 IgG4-RD patients"

Case WBC/
(×109/L)		 EO% EO/
(×109/L)		 IgE/
(IU/mL)		 IgA/
(g/L)		 IgM/
(g/L)		 IgG/
(g/L)		 IgG4/
(mg/dL)		 C3/
(g/L)		 C4/
(g/L)		 ESR/
(mm/h)		 CRP/
(mg/L)		 ANA
1 13.97 9.3 1.29 359.7 0.94 0.435 31.2 4 370 0.846 0.314 19 3.30 -
2 8.20 1.1 0.09 ND 1.83 0.400 9.5 225 0.780 0.170 2 2.43 -
3 8.10 3.9 0.30 391.0 1.42 0.756 7.3 341 0.858 0.192 3 <0.50 -
4 9.30 2.5 0.20 206.6 1.38 0.627 16.4 1 880 0.748 0.149 8 0.39 1 :80
homogenesis
5 7.06 7.4 0.52 596.8 1.23 0.754 23.2 2 510 0.654 0.238 53 1.80 -
6 DL DL DL 221.0 DL DL DL 3 270 DL DL DL DL DL
7 5.40 1.0 0.10 ND 1.99 0.663 11.7 207 0.900 0.155 2 2.47 -
8 9.79 1.5 0.15 1 040.0 6.74 0.875 18.4 431 0.845 0.166 ND 10.90 -
9 11.20 0.2 0 1 164.0 1.80 0.329 52.7 6 100 0.455 0.040 32 <0.50 -
10 10.70 0.1 0 12.2 0.95 0.754 7.3 153 0.972 0.285 57 90.10 -

Figure 1

Imaging examination characteristics of IgG4-RD patients (cranial MRI) A, pituitary stalk thickened in case 3(arrow); B, dura mater thickened and enhanced in case 10(arrow). IgG4-RD, immunoglobulin G4-related disease."

Table 3

Imaging examination, histopathology and treatment of 10 IgG4-RD patients"

Case Imaging examination Histopathology Induction
therapy		 Outcome Follow-up/
month		 Relapse
Biopsy tissue LI TF OP IgG4+/
HPF		 IgG4+/
IgG+
1 Pituitary gland plumped SMG + - - >10 50% GC+CTX PR 76 N
2 Sellar space occupied ND ND ND ND ND ND GC+CTX PR 42 N
3 Pituitary stalk thickened LN + - - >50 20% GC+CTX/RTX PR 14 N
4 Pituitary stalk thickened Pars orbitalis + - - >20 40% GC+CTX/
MMF/RTX		 PR 13 Y
5 Abnormal signal in pituitary, cerebellar tentorium thickened, bilateral cavernous sinus enlarged Pancreas + + + >50 80% GC+AZA CR 108 N
6 Circular nodules in pituitary LN + - - >50 40% GC CR 12 N
7 Dura mater thickened and enhanced, dural nodules Right frontal
parietal lobe		 + + - 30 40% GC+CTX PR 6 N
8 Dura mater thickened, optic nerve thickened ND ND ND ND ND ND GC+RTX PR 48 Y
9 Dura mater thickened, right caver-nous sinus occupied Sious
cavernosus		 + + - 30 40% GC+CTX PR 9 Y
10 Dura mater thickened and enhanced, spinal dura mater thickened Meninges + + - >10 40% GC+CTX PR 5 Y

Figure 2

Histopathologic features of IgG4-RD patients (HE ×200) Fibrous tissue hyperplasia, a large number of lymphocytes and plasma cells infiltration (case 7). IgG4-RD, immunoglobulin G4-related disease."

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