IgG4-related disease (IgG4-RD) is a disorder with various clinical manifestations. Central nervous system (CNS) involvement is well recognized, with hypertrophic pachymeningitis and hypophysitis being the most common manifestations. Spinal cord involvement is an extremely rare manifestation. We present the first case of an IgG4-RD patient with spinal cord parenchymal disease and concurrent hypophysitis. We review also the current literature about CNS parenchymal involvement in the context of IgG4-RD. A young female presented with clinical symptoms of myelitis. Cervical spinal cord magnetic resonance imaging (MRI) displayed features of longitudinally extensive transverse myelitis (LETM). Brain MRI showed a small number of high-intensity lesions in the deep white matter and enlargement of hypophysis with homogeneous gadolinium enhancement (asymptomatic hypophysitis). Diagnostic workup revealed elevated IgG4 serum levels (146 mg/dL). Our patient fulfilled the organ-specific diagnostic criteria of IgG4-hypophysitis. Treatment with intravenous glucocorticoids led to rapid clinical response, and to the substantial resolution of imaging findings. Azathioprine was used as a maintenance treatment. One relapse occurred 2 years after the initial diagnosis and patient was re-treated with glucocorticoids. Three years after relapse, patient is in remission with azathioprine. We present the first case of myelitis with radiological features of LETM associated with increased IgG4 serum levels and the simultaneous presence of asymptomatic IgG4-related hypophysitis.
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Central nervous system
Myelin oligodendrocyte glycoprotein
Neuromyelitis optica spectrum disorders
Longitudinally extensive transverse myelitis
Bozzalla Cassione E, Stone JH (2017) IgG4-related disease. Curr Opin Rheumatol 29:223–227. https://doi.org/10.1097/bor.0000000000000383
Carruthers MN, Topazian MD, Khosroshahi A, Witzig TE, Wallace ZS, Hart PA, Deshpande V, Smyrk TC, Chari S, Stone JH (2015) Rituximab for IgG4-related disease: a prospective, open-label trial. Ann Rheum Dis 74:1171–1177. https://doi.org/10.1136/annrheumdis-2014-206605
Wallace ZS, Zhang Y, Perugino CA, Naden R, Choi HK, Stone JH, Committee AEI-RCC (2019) Clinical phenotypes of IgG4-related disease: an analysis of two international cross-sectional cohorts. Ann Rheum Dis 78:406–412. https://doi.org/10.1136/annrheumdis-2018-214603
AbdelRazek MA, Venna N, Stone JH (2018) IgG4-related disease of the central and peripheral nervous systems. Lancet Neurol 17:183–192. https://doi.org/10.1016/s1474-4422(17)30471-4
Baptista B, Casian A, Gunawardena H, D'Cruz D, Rice CM (2017) Neurological manifestations of IgG4-related disease. Curr Treat Options Neurol 19:14. https://doi.org/10.1007/s11940-017-0450-9
Deshpande V, Zen Y, Chan JK, Yi EE, Sato Y, Yoshino T, Kloppel G, Heathcote JG, Khosroshahi A, Ferry JA, Aalberse RC, Bloch DB, Brugge WR, Bateman AC, Carruthers MN, Chari ST, Cheuk W, Cornell LD, Fernandez-Del Castillo C, Forcione DG, Hamilos DL, Kamisawa T, Kasashima S, Kawa S, Kawano M, Lauwers GY, Masaki Y, Nakanuma Y, Notohara K, Okazaki K, Ryu JK, Saeki T, Sahani DV, Smyrk TC, Stone JR, Takahira M, Webster GJ, Yamamoto M, Zamboni G, Umehara H, Stone JH (2012) Consensus statement on the pathology of IgG4-related disease. Mod Pathol 25:1181–1192. https://doi.org/10.1038/modpathol.2012.72
De Virgilio A, de Vincentiis M, Inghilleri M, Fabrini G, Conte M, Gallo A, Rizzo MI, Greco A (2017) Idiopathic hypertrophic pachymeningitis: an autoimmune IgG4-related disease. Immunol Res 65:386–394. https://doi.org/10.1007/s12026-016-8863-1
Khosroshahi A, Wallace ZS, Crowe JL, Akamizu T, Azumi A, Carruthers MN, Chari ST, Della-Torre E, Frulloni L, Goto H, Hart PA, Kamisawa T, Kawa S, Kawano M, Kim MH, Kodama Y, Kubota K, Lerch MM, Lohr M, Masaki Y, Matsui S, Mimori T, Nakamura S, Nakazawa T, Ohara H, Okazaki K, Ryu JH, Saeki T, Schleinitz N, Shimatsu A, Shimosegawa T, Takahashi H, Takahira M, Tanaka A, Topazian M, Umehara H, Webster GJ, Witzig TE, Yamamoto M, Zhang W, Chiba T, Stone JH (2015) International consensus guidance statement on the management and treatment of IgG4-related disease. Arthritis Rheumatol 67:1688–1699. https://doi.org/10.1002/art.39132
Lin J, Zheng L, Zhou D, Hong Z (2019) Immunoglobulin G4-related disease involving both cerebral parenchyma and spinal cord: a case report. J Neuroimmunol 335:577018. https://doi.org/10.1016/j.jneuroim.2019.577018
Kim EH, Kim SH, Cho JM, Ahn JY, Chang JH (2011) Immunoglobulin G4-related hypertrophic pachymeningitis involving cerebral parenchyma. J Neurosurg 115:1242–1247. https://doi.org/10.3171/2011.7.jns1166
Li LF, Tse PY, Tsang FC, Lo RC, Lui WM, Leung GK (2015) IgG4-related hypertrophic pachymeningitis at the falx cerebrii with brain parenchymal invasion: a case report. World Neurosurg 84(591):e597–e610. https://doi.org/10.1016/j.wneu.2015.03.035
Moss HE, Mejico LJ, de la Roza G, Coyne TM, Galetta SL, Liu GT (2012) IgG4-related inflammatory pseudotumor of the central nervous system responsive to mycophenolate mofetil. J Neurol Sci 318:31–35. https://doi.org/10.1016/j.jns.2012.04.010
Sireesha Y, Uppin MS, Ganti S, Alugolu R, Mudumba VS, Bhattacharjee S, Neeharika ML, Bastia J, Kanikannan MA (2019) A series of biopsy-proven patients with immunoglobulin G4-related neurological disease. Ann Indian Acad Neurol 22:73–78. https://doi.org/10.4103/aian.aian_283_18
Tanji H, Okada H, Igari R, Yamaguchi Y, Sato H, Takahashi Y, Koyama S, Arawaka S, Wada M, Kawanami T, Wakabayashi K, Kato T (2016) Inflammatory pseudotumor of the brain parenchyma with IgG4 hypergammaglobulinemia. Intern Med 55:1911–1916. https://doi.org/10.2169/internalmedicine.55.5854
Wu PC, Tien PT, Li YH, Chen RY, Cho DY (2017) IgG4-related cerebral pseudotumor with perineural spreading along branches of the trigeminal nerves causing compressive optic neuropathy: a case report. Medicine (Baltimore) 96:e8709. https://doi.org/10.1097/md.0000000000008709
Regev K, Nussbaum T, Cagnano E, Giladi N, Karni A (2014) Central nervous system manifestation of IgG4-related disease. JAMA Neurol 71:767–770. https://doi.org/10.1001/jamaneurol.2014.40
Lui PC, Fan YS, Wong SS, Chan AN, Wong G, Chau TK, Tse GM, Cheng Y, Poon WS, Ng HK (2009) Inflammatory pseudotumors of the central nervous system. Hum Pathol 40:1611–1617. https://doi.org/10.1016/j.humpath.2009.04.016
Boban J, Ardali S, Thurnher MM (2018) Leptomeningeal form of Immunoglobulin G4-related hypertrophic meningitis with perivascular spread: a case report and review of the literature. Neuroradiology 60:769–773. https://doi.org/10.1007/s00234-018-2028-y
Ekizoglu E, Coban O, Ulukan C, Gezen Ak D, Dursun E, Tuzun E, Baykan B (2018) Intracranial hypertension related to cerebral venous thrombosis; and acute ischemic stroke with micro-infarcts associated with IgG4-related disease. Int J Neurosci 128:1097–1099. https://doi.org/10.1080/00207454.2018.1458728
Toyoshima Y, Emura I, Umeda Y, Fujita N, Kakita A, Takahashi H (2012) Vertebral basilar system dolichoectasia with marked infiltration of IgG4-containing plasma cells: a manifestation of IgG4-related disease? Neuropathology 32:100–104. https://doi.org/10.1111/j.1440-1789.2011.01227.x
Usami T, Kawashima S, Ueki Y, Toyoda T, Okita K, Matsukawa N (2018) Early treatment for IgG4-related disease may prevent cognitive impairment caused by cerebral vasculitis: a case report and review of the literature. eNeurologicalSci 10:45–47. https://doi.org/10.1016/j.ensci.2017.12.005
Joshi D, Jager R, Hurel S, Pereira SP, Johnson GJ, Chapman M, Fowler R, Winstanley A, Losseff N, Webster GJ (2015) Cerebral involvement in IgG4-related disease. Clin Med (Lond) 15:130–134. https://doi.org/10.7861/clinmedicine.15-2-130
Lu LX, Della-Torre E, Stone JH, Clark SW (2014) IgG4-related hypertrophic pachymeningitis: clinical features, diagnostic criteria, and treatment. JAMA Neurol 71:785–793. https://doi.org/10.1001/jamaneurol.2014.243
Ezzeldin M, Shawagfeh A, Schnadig V, Smith RG, Fang X (2014) Hypertrophic spinal pachymeningitis: idiopathic vs. IgG4-related. J Neurol Sci 347:398–400. https://doi.org/10.1016/j.jns.2014.10.012
Kiefer D, Kiltz U, Braun J (2019) Chronic back pain, cervicothoracic myeolopathy and weight loss—a case report of an IgG4-related disease. Dtsch Med Wochenschr 144:965–968. https://doi.org/10.1055/a-0850-0600
Mohanasundaram K, Mahendran B, Mani M, Saravanan M, Rajeswari S (2016) Compressive myelopathy: a rare clinical presentation of IgG4-related disease. Indian J Rheumatol 11:222–225
Slade SJ, Bauer EM, Stone VV, Dave AJ (2019) Spinal IgG4-related hypertrophic pachymeningitis with spinal cord compression: case report and literature review. World Neurosurg 130:65–70. https://doi.org/10.1016/j.wneu.2019.06.130
Wallace ZS, Carruthers MN, Khosroshahi A, Carruthers R, Shinagare S, Stemmer-Rachamimov A, Deshpande V, Stone JH (2013) IgG4-related disease and hypertrophic pachymeningitis. Medicine (Baltimore) 92:206–216. https://doi.org/10.1097/md.0b013e31829cce35
Kanagaraju V, Rai D, Alluri RV, Prasanna C, Shyam Sundar V, Arvind Kumar SM, Venkatesh Kumar N (2016) An inflammatory pseudotumor in the thoracic epidural space presenting with progressive paraplegia: a histopathological diagnosis with clinical and radiological uncertainty. Case report with literature review. Eur Spine J 25 Suppl 1:75–79. https://doi.org/10.1007/s00586-015-4106-8
Bridges KJ, DeDeaux CH, Than KD (2019) IgG4-related disease presenting as intradural extramedullary lesion: a case report and review of the literature. Br J Neurosurg 33:570–576. https://doi.org/10.1080/02688697.2017.1384793
Maher M, Zanazzi G, Faust P, Nickerson K, Wong TT (2017) IgG4-related hypertrophic pachymeningitis of the spine with MPO-ANCA seropositivity. Clin Imaging 46:108–112. https://doi.org/10.1016/j.clinimag.2017.07.012
Radotra BD, Aggarwal A, Kapoor A, Singla N, Chatterjee D (2016) An orphan disease: IgG4-related spinal pachymeningitis: report of 2 cases. J Neurosurg Spine 25:790–794. https://doi.org/10.3171/2016.4.spine1674
Rumalla K, Smith KA, Arnold PM (2017) Immunoglobulin G4-related epidural inflammatory pseudotumor presenting with pulmonary complications and spinal cord compression: case report. J Neurosurg Spine 26:688–693. https://doi.org/10.3171/2016.11.spine16924
Winkel M, Lawton CD, Sanusi OR, Horbinski CM, Dahdaleh NS, Smith ZA (2018) Neuro-surgical considerations for treating IgG4-related disease with rare spinal epidural compression. Surg Neurol Int 9:209. https://doi.org/10.4103/sni.sni_156_18
Melenotte C, Seguier J, Ebbo M, Kaphan E, Bernit E, Saillier L, Audoin B, Feyeux D, Daniel L, Roche PH, Graillon T, Dufour H, Boutiere C, Girard N, Closs-Prophette F, Guillaud C, Tieulie N, Regent A, Harle JR, Hamidou M, Mekinian A, Grados A, Schleinitz N (2019) Clinical presentation, treatment and outcome of IgG4-related pachymeningitis: from a national case registry and literature review. Semin Arthritis Rheum. https://doi.org/10.1016/j.semarthrit.2019.05.003
van den Elshout-den UD, Spoto CPE, de Boer M, Leiner T, Leavis HL, Leguit RJ (2019) First report of IgG4 related disease primary presenting as vertebral bone marrow lesions. Front Immunol 10:1910. https://doi.org/10.3389/fimmu.2019.01910
Leporati P, Landek-Salgado MA, Lupi I, Chiovato L, Caturegli P (2011) IgG4-related hypophysitis: a new addition to the hypophysitis spectrum. J Clin Endocrinol Metab 96:1971–1980. https://doi.org/10.1210/jc.2010-2970
Hattori Y, Tahara S, Ishii Y, Kitamura T, Inomoto C, Osamura RY, Teramoto A, Morita A (2013) A case of IgG4-related hypophysitis without pituitary insufficiency. J Clin Endocrinol Metab 98:1808–1811. https://doi.org/10.1210/jc.2013-1088
Kitley JL, Leite MI, George JS, Palace JA (2012) The differential diagnosis of longitudinally extensive transverse myelitis. Mult Scler 18:271–285. https://doi.org/10.1177/1352458511406165
Tan CT, Mao Z, Qiu W, Hu X, Wingerchuk DM, Weinshenker BG (2016) International consensus diagnostic criteria for neuromyelitis optica spectrum disorders. Neurology 86:491–492. https://doi.org/10.1212/wnl.0000000000002366
The authors express their gratitude to the patient for allowing her data to be used for research purposes.
No funding was obtained for the preparation of this case report.
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Author GE Fragoulis has received travelling Grants from Abbvie. All the other authors declare that they have no conflict of interests.
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Vakrakou, A.G., Evangelopoulos, M., Boutzios, G. et al. Recurrent myelitis and asymptomatic hypophysitis in IgG4-related disease: case-based review. Rheumatol Int 40, 337–343 (2020). https://doi.org/10.1007/s00296-019-04502-6
- IgG4-related disease
- Longitudinally extensive transverse myelitis (LETM)
- Magnetic resonance imaging (MRI)