Ghassen Gader1, Fatma Ben Atig2, Nesrine Jemel1, Malek Bourgou1, Abdelhafidh Slimane2, Khalil Ghedira2, Mohamed Badri1, Ihsèn Zammel1
  1. Department of Neurosurgery, Trauma and Burns Center, Ben Arous, Tunisia.
  2. Department of Neurosurgery, National Institute of Neurology, Tunis, Tunisia.

Correspondence Address:
Ghassen Gader, Department of Neurosurgery, Trauma and Burns Center, Ben Arous, Tunisia.


Copyright: © 2023 Surgical Neurology International This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-Share Alike 4.0 License, which allows others to remix, transform, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.

How to cite this article: Ghassen Gader1, Fatma Ben Atig2, Nesrine Jemel1, Malek Bourgou1, Abdelhafidh Slimane2, Khalil Ghedira2, Mohamed Badri1, Ihsèn Zammel1. Epiduritis related to IgG4 disease: A very rare cause for spinal cord compression. 16-Jun-2023;14:205

How to cite this URL: Ghassen Gader1, Fatma Ben Atig2, Nesrine Jemel1, Malek Bourgou1, Abdelhafidh Slimane2, Khalil Ghedira2, Mohamed Badri1, Ihsèn Zammel1. Epiduritis related to IgG4 disease: A very rare cause for spinal cord compression. 16-Jun-2023;14:205. Available from:

Date of Submission

Date of Acceptance

Date of Web Publication


Background: Inflammatory pseudotumors are rare, and those attributed to immunoglobulin G4 (IgG4) diseases are even less frequently encountered. Here, we reviewed 41 cases from the literature of spinal inflammatory pseudotumors due to IgG4 and have added our single new case.

Case Presentation: A 25-year-old male presented with progressive back pain, bilateral paraparesis, and sphincter dysfunction. His deficit was attributed to MR-documented posterolateral lesion between the T5 and T10 levels for which he levels underwent a T1–T1010 laminectomy. The pathology revealed an immunoglobulin G4-related inflammatory pseudotumor. Postoperatively, the patient additionally required systemic and epidural administration of glucocorticoids.

Conclusion: IgG4-related disease is an emerging clinical condition that rarely involves the central nervous system. Spinal inflammatory pseudotumors, including IgG4 disease, should be more commonly considered among the potential differential diagnoses of lesions compressing the spinal cord.

Keywords: Epiduritis, Inflammation, Neurosurgery, Spinal cord, Spine surgery


Immunoglobulin G4-related disease (IgG4-RD) is a fibroinflammatory disease characterized by sclerosing tumefactions and organ enlargement attributed to increased infiltration of lymphocytes and plasma cells (i.e., mainly into the pancreas, liver, salivary, and lacrimal glands, but rarely the kidneys, bile duct, and thyroid gland).[ 16 , 38 ] The central nervous system (CNS) is a very rare location for IgG4-RD lesions.[ 14 , 35 ] Here, we report a very rare case of radiologically-documented spinal cord compression between the T5 and T10 levels attributed to pachymeningitis caused by IgG4 disease that favorably responded to decompression.


A 25-year-old male presented with 2 months of progressive upper back pain radiating around his trunk. However, within the past 7 days, he rapidly developed paraparesis (3/5 level), a relative T6 pin level and dysuria. The thoracic magnetic resonance imaging (MRI) [ Figure 1 ] showed posterolateral epiduritis between the T5 and T10 levels contributing to marked cord compression; it was isointense on T1, slightly hyperintense on T2-weighted images, and markedly enhanced with contrast. The patient underwent and emergent T5–T10 laminectomy. As surgery, the lesion appeared soft, yellowish, and there was a clear cleavage plane between tumor and the dura mater; gross total resection was readily achieved. The patient’s postoperative course was uneventful; he fully recovered motor, sensory, and urological function and was discharged on the 5th postoperative day.

Figure 1:

Sagittal (a) and axial (b) sections of a spinal cord magnetic resonance imaging on T1-weighted image with injection of Gadolinium showing a posterior epiduritis ranging from T5 to T10 responsible for compression of the spinal cord.



The pathological examination [ Figure 2 ] revealed diffuse infiltration of inflammatory cells within the fibrofatty tissue, accompanied by 50 IgG4+ cells/HPF and 50% IgG4+/IgG cell ratio. The serum level of IgG4 was 151 mg/dL. High serum IgG4 levels and immunohistopathological findings fulfilled the criteria for the diagnosis of a IgG4-RD lesion. Thus, the patient was placed on 0.6 mg/kg/d of methylprednisolone for the first 15 days postoperatively, followed later by a tapering dosage.

Figure 2:

Pathological examination showing a diffuse infiltration of inflammatory cells within the fibrofatty tissue, with presence of 50 immunoglobulin G4 (IgG4)+ cells/high-powered field and 50% IgG4+/IgG cell ratio.



Frequency and location of IgG4-RD

IgG4-RD usually occurs in middle-aged patients (50–60 years) and demonstrates a significant male predominance.[ 38 ] It is a rare chronic inflammatory autoimmune disease which may affect almost any organ. It may also present as a single or multiorgan disease. It mostly occurs in the pancreas, salivary glands, and lacrimal glands. Only rarely is IgG4-RD found in the CNS where it mainly presents as a hypertrophic pachymeningitis and/ or hypophysitis.[ 2 , 13 , 29 , 39 , 47 ] Notably, spinal pachymeningitis leading to spinal cord compression is extremely rare; we were only able to identify 41such cases in the literature [ Table 1 ].

Table 1:

Table summarizing all previously reported cases of spinal epiduritis related to an IgG4 disease.[ 1 , 3 - 9 , 11 - 13 , 15 , 19 - 28 , 30 - 34 , 37 , 40 - 49]


Pathological diagnosis of CNS IgG4-RD

Although immunohistochemistry is the gold standard for establishing the accurate diagnosis of IgG4 cells ratios, other major histopathological confirmatory features include lymphoplasmacytic infiltrates, fibrosis, and obliterative phlebitis.[ 10 ]

Radiological features for diagnosing CNS IgG4-RD

The radiological features for diagnosing CNS IgG4-RD are nonspecific. In fact, pathology may mistakenly lead to the diagnosis of other granulomatous diseases, such as lymphoma or even metastatic epiduritis.[ 2 , 20 ]

Surgical indications with the onset of neurological impairment

Emergent surgical decompression may be warranted when spinal pachymeningitis related to IgG4 disease causes neurologic impairment. Certainly, the spinal cord compression from IgG4 can be readily treated with emergent decompressive laminectomy with or without fusion. Although gross total excision is optimal, more restricted tumor removal may be dictated by critical adjacent structures.

No strict protocols to treat IgG4-RD lesions

As spinal pachymeningitis related to IgG4 disease is rare, there are no specific therapeutic protocols available.[ 14 , 47 ] Typically patients are first treated with systemic corticosteroids for at least 1 year.[ 17 , 36 ] Although lesions may recur following incomplete resection, they are more frequently encountered inpatients who did not receive adjuvant postoperative steroids. Further, immunosuppressive therapy may be warranted in patients showing systemic involvement.[ 17 , 18 ]


Inflammatory CNS IgG-RD lesions should be considered among the differential diagnoses for patients presenting with spinal cord compression.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.


The views and opinions expressed in this article are those of the authors and do not necessarily reflect the official policy or position of the Journal or its management. The information contained in this article should not be considered to be medical advice; patients should consult their own physicians for advice as to their specific medical needs.


1. Alrashdi MN. Immunoglobulin G4-related spinal pachymeningitis. Saudi Med J. 2020. 41: 652-6

2. Baptista B, Casian A, Gunawardena H, D’Cruz D, Rice CM. Neurological manifestations of IgG4-related disease. Curr Treat Options Neurol. 2017. 19: 14

3. Bridges KJ, DeDeaux CH, Than KD. IgG4-related disease presenting as intradural extramedullary lesion: A case report and review of the literature. Br J Neurosurg. 2019. 33: 570-6

4. Cação G, Calejo M, Alves J, Medeiros P, Vila-Cha N, Mendonça T. Clinical features of hypertrophic pachymeningitis in a center survey. Neurol Sci. 2019. 40: 543-51

5. Chan SK, Cheuk W, Chan KT, Chan JK. IgG4-related sclerosing pachymeningitis: A previously unrecognized form of central nervous system involvement in IgG4-related sclerosing disease. Am J Surg Pathol. 2009. 33: 1249-52

6. Chen H, Gnepp D, Paul J, Borra S. A mysterious back pain. J Postgrad Med. 2014. 60: 61-8

7. Choi SH, Lee SH, Khang SK, Jeon SR. IgG4-related sclerosing pachymeningitis causing spinal cord compression. Neurology. 2010. 75: 1388-90

8. Della-Torre E, Bozzolo E, Passerini G, Doglioni C, Sabbadini M. IgG4-related pachymeningitis: Evidence of intrathecal IgG4 on cerebrospinal fluid analysis. Ann Intern Med. 2012. 156: 401-3

9. Della-Torre E, Galli L, Franciotta D, Bozzolo EP, Briani C, Furlan R. Diagnostic value of IgG4 indices in IgG4-related hypertrophic pachymeningitis. J Neuroimmunol. 2014. 266: 82-6

10. Deshpande V, Zen Y, Chan J, Yi E, Sato Y, Yoshino T. Consensus statement on the pathology of IgG4-related disease. Mod Pathol. 2012. 25: 1181-92

11. Ezzeldin M, Shawagfeh A, Schnadig V, Smith R, Fang X. Spinal cord compression associated with a systemic IgG4 disease. Neurology. 2014. 82: 25-30

12. Fernandez-Codina A, Hernandez-Gonzalez M, Solans-Laquè R, Bujan-Rivas S, Vilardell-Tarrés M, Martinez-Valle F. Alteration of IgG4 levels in cerebrospinal fluid in IgG4-related disease. Int J Rheum Dis. 2017. 20: 1865-7

13. Ferreira NR, Vaz R, Carmona S, Mateus S, Pereira P, Fernandes L. IgG4-related disease presenting with an epidural inflammatory pseudotumor: A case report. J Med Case Rep. 2016. 10: 61

14. Goulam-Houssein S, Grenville JL, Mastrocostas K, Munoz DG, Lin A, Bharatha A. IgG4-related intracranial disease. Neuroradiol J. 2019. 32: 29-35

15. Gu R, Hao P, Liu J, Wang Z, Zhu Q. Cervicothoracic spinal cord compression caused by IgG4-related sclerosing pachymeningitis: A case report and literature review. Eur Spine J. 2016. 25: 147-51

16. Kamisawa T, Funata N, Hayashi Y, Eishi Y, Koike M, Tsuruta K. A new clinicopathological entity of IgG4-related autoimmune disease. J Gastroenterol. 2003. 38: 982-4

17. Khosroshahi A, Wallace ZS, Crowe JL, Akamizu T, Azumi A, Carruthers MN. International consensus guidance statement on the management and treatment of IgG4-related disease. Arthritis Rheumatol. 2015. 67: 1688-99

18. Khosroshahi A, Carruthers MN, Deshpande V, Unizony S, Bloch DB, Stone JH. Rituximab for the treatment of IgG4-related disease: Lessons from 10 consecutive patients. Medicine (Baltimore). 2012. 91: 57-66

19. Kim SH, Kang Y, Oh SH, Paik S, Kim JS. Paraplegia in a patient with IgG4-related sclerosing disease: A case report. Ann Rehabil Med. 2014. 38: 856-60

20. Kramer DE, Kerolus MG, Furlan K, Nag S, O’Toole JE. Recurrent IgG4-related meningeal disease of the cervicothoracic spine: A case report and review of the literature. Neurol India. 2022. 70: 1180-6

21. Levraut M, Cohen M, Bresch S, Giordana C, BruelVandenbos F, Mondot L. Immunoglobulin G4-related hypertrophic pachymeningitis: A case-oriented review. Neurol Neuroimmunol Neuroinflamm. 2019. 6: e568

22. Li HX, Zuo L, Peng XX, Zong Q, Zhang K, Liu YZ. Immunoglobulin G4-related hypertrophic pachymeningitis with spinal cord compression: A case report. J Neuroimmunol. 2020. 347: 577325

23. Lindstrom KM, Cousar JB, Lopes MB. IgG4-related meningeal disease: Clinicopathological features and proposal for diagnostic criteria. Acta Neuropathol (Berl). 2010. 120: 765-76

24. Lu Z, Tongxi L, Jie L, Yujuan J, Wei J, Xia L. IgG4-related spinal pachymeningitis. Clin Rheumatol. 2016. 35: 1549-53

25. Maher M, Zanazzi G, Faust P, Nickerson K, Wong T. IgG4-related hypertrophic pachymeningitis of the spine with MPOANCA seropositivity. Clin Imaging. 2017. 46: 108-12

26. Melenotte C, Seguier J, Ebbo M, Kaphan E, Bernit E, Saillier L. Clinical presentation, treatment and outcome of IgG4-related pachymeningitis: From a national case registry and literature review. Semin Arthritis Rheum. 2019. 49: 430-7

27. Merza N, Taha A, Lung J, Benderman AW, Wright SE. IgG4-related sclerosing disease causing spinal cord compression: The first reported case in literature. Case Rep Immunol. 2019. 2019: 3618510

28. Radotra BD, Agrawal A, Kapoor A, Singla N, Chatterjee D. An orphan disease: IgG4-related spinal pachymeningitis: Report of 2 cases. J Neurosurg Spine. 2016. 25: 790-4

29. Regev K, Nussbaum T, Cagnano E, Giladi N, Karni A. Central nervous system manifestation of IgG4-related disease. JAMA Neurol. 2014. 71: 767-70

30. Rumalla K, Smith K, Arnold P. Immunoglobulin G4-related epidural inflammatory pseudotumor presenting with pulmonary complications and spinal cord compression: Case report. J Neurosurg Spine. 2017. 26: 688-93

31. Sakai T, Kondo M, Yoshii S, Tomimoto H. IgG4-related disease that presented cranial, cervical, lumbar and sacral hypertrophic pachymeningitis associated with infundibulo-hypophysitis. Rinsho Shinkeigaku. 2014. 54: 664-7

32. Sbeih I, Darawazeh R, Shehadeh M, Al-Kanash R, AbuFarsakh H, Sbeih A. Immunoglobulin G4-related hypertrophic pachymeningitis of the spine: A case report and systematic review of the literature. World Neurosurg. 2020. 143: 445-53

33. Sireesha Y, Uppin M, Ganti S, Aluoglu R, Mudumba V, Bhattacharjee S. A series of biopsy-proven patients with immunoglobulin G4-related neurological disease. Ann Indian Acad Neurol. 2019. 22: 73-8

34. Slade SJ, Bauer EM, Stone VV, Dave AJ. Spinal IgG4-related hypertrophic pachymeningitis with spinal cord compression: Case report and literature review. World Neurosurg. 2019. 130: 65-70

35. Stone JH, Deshpande V. IgG4-related disease. N Engl J Med. 2012. 366: 539-51

36. Stone JH, Khosroshahi A, Deshpande V, Chan JK, Heathcote JG, Aalberse R. Recommendations for the nomenclature of IgG4-related disease and its individual organ system manifestations. Arthritis Rheum. 2012. 64: 3061-7

37. Tajima Y, Mito Y. Cranial neuropathy because of IgG4-related pachymeningitis; intracranial and spinal mass lesions. BMJ Case Rep. 2012. 19: bcr2012006471

38. Takahashi H, Yamamoto M, Suzuki C, Naishiro Y, Shinomura Y, Imai K. The birthday of a new syndrome: IgG4-related diseases constitute a clinical entity. Autoimmun Rev. 2010. 9: 591-4

39. Tanji H, Okada H, Igari R, Yamaguchi Y, Sato H, Takahashi Y. Inflammatory pseudotumor of the brain parenchyma with IgG4 hypergammaglobulinemia. Intern Med. 2016. 55: 1911-6

40. Umehara H, Okazaki K, Masaki Y, Kawano M, Yamamoto M, Saeki T. A novel clinical entity, IgG4-related disease (IgG4RD): General concept and details. Mod Rheumatol. 2012. 22: 1-14

41. Varrassi M, Gianneramo C, Arrigoni F, Cerrone P, Sucapane P, Marini C. Neurological involvement of IgG4-related disease: Description of a case and review of the literature. Neuroradiol J. 2018. 31: 196-202

42. Wallace ZS, Carruthers MN, Khosorshahi A, Carruthers R, Shingare S, Stemmer-Rachamimov A. IgG4-related disease and hypertrophic pachymeningitis. Medicine (Baltimore). 2013. 92: 206-16

43. Williams MM, Mashaly H, Puduvalli VK, Jin M, Mendel E. Immunoglobulin G4-related disease mimicking an epidural spinal cord tumor: Case report. J Neurosurg Spine. 2017. 26: 76-80

44. Winkel M, Lawton CD, Sanusi OR, Horbinski CM, Dahdaleh NS, Smith ZA. Neuro-surgical considerations for treating IgG4-related disease with rare spinal epidural compression. Surg Neurol Int. 2018. 9: 209

45. Yangue Y, Gambaracci G, Floridi P, Fiacca A, Guerreiro A, Giansanti M. IgG4-related cranio-spinal hypertrophic pachymeningitis involving the internal auditory canal. J Biol Regul Homeost Agents. 2016. 30: 915-9

46. Zhang R, Gao J, Zhao T, Zhang B, Wang C, Wang C. A case with IgG4-related spinal pachymeningitis causing spinal cord compression. Front Neurol. 2020. 11: 500

47. Zhang Z, Fu W, Wang M, Niu L, Liu B, Jiao Y. IgG4-related inflammatory pseudotumor of the brain parenchyma: A case report and literature review. Acta Neurol Belg. 2018. 118: 617-27

48. Zhao Q, Dong A, Bai Y, Wang Y, Zuo C. FDG PET/ CT in immunoglobulin G4-related spinal hypertrophic pachymeningitis. Clin Nucl Med. 2017. 42: 958-61

49. Zwicker J. IgG4-related disease presenting as dural thickening-a rare cause of myelopathy. Can J Neurol Sci. 2014. 41: 392-6

Leave a Reply

Your email address will not be published. Required fields are marked *