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 Table of Contents  
Year : 2022  |  Volume : 2  |  Issue : 4  |  Page : 980-983

Childhood IgG4-related orbital disease: A delayed diagnosis

1 Department of Oculoplasty and Ocular Oncology, All India Institute of Medical Sceinces, New Delhi, India
2 Department of Ocular Pathology, All India Institute of Medical Sceinces, New Delhi, India
3 Pediatric Ophthalmology, Chacha Nehru Bal Chikitsalaya, New Delhi, India
4 Department of Radiology Dr Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sceinces, New Delhi, India

Date of Submission03-Mar-2022
Date of Acceptance26-Jul-2022
Date of Web Publication11-Oct-2022

Correspondence Address:
Dr. Meenakshi Wadhwani
Chacha Nehru Bal Chikitsalya, New Delhi
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijo.IJO_481_22

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IgG4-related disease is a multisystem disorder characterized by tumefactive lesions comprising of IgG4-bearing plasma cells with fibrosis. We report a case of pediatric IgG4-related orbital disease that was diagnosed 12 years after its first clinical manifestation and we present sequential imaging findings of the case.

Keywords: IGg4, inflammatory orbital disease, proptosis

How to cite this article:
Meel R, Kashyap S, Wadhwani M, Bajaj MS, Sharma SS. Childhood IgG4-related orbital disease: A delayed diagnosis. Indian J Ophthalmol Case Rep 2022;2:980-3

How to cite this URL:
Meel R, Kashyap S, Wadhwani M, Bajaj MS, Sharma SS. Childhood IgG4-related orbital disease: A delayed diagnosis. Indian J Ophthalmol Case Rep [serial online] 2022 [cited 2022 Nov 27];2:980-3. Available from: https://www.ijoreports.in/text.asp?2022/2/4/980/358174

IgG4-related orbital disease (IgG4ROD) is a newly recognized clinical entity characterized by tumefactive lesions that show lympho-plasmocytic infiltrate rich in polyclonal IgG4 plasma cells on histopathological examination (HPE), with or without raised serum IgG4 levels.[1] There are only a few case reports on pediatric IgG4ROD (pIgG4ROD) reported in literature. Herein, we present the clinicoradiological findings of a case of pIgG4ROD over a 12-year duration.

  Case Report Top

A 24-year-old male presented with diminution of vision (DOV) in the right eye for 15 days. There was history of DOV in the left eye at 12 years of age for which he was seen by an ophthalmologist and neurosurgeon. Clinical records available with the patient, revealed perception of light and complete restriction of extraocular movements (EOM) OS with bilateral proptosis at that time. Incisional biopsy (IB) performed 12 years ago showed fibro-collagenous tissue with multiple foci of lymphoid collection comprising of mature lymphocytes and plasma cells. A diagnosis of inflammatory orbital disease (IOI) was made, and the patient was treated with oral steroids but no clinical improvement was observed. Review of old imaging (contrast-enhanced magnetic resonance imaging [CEMRI]) revealed ill-defined, moderately enhancing mass lesion in the inferior and lateral extraconal spaces of the right orbit, involving the orbital apex and extending to the ipsilateral cavernous sinus, infra-temporal fossa, and masticator space. A similar lesion was noted in the left orbital apex. The lesions were isointense to brain on T1-weighted MRI and markedly hypointense on T2-weighted MRI [Figure 1]a,[Figure 1]b,[Figure 1]c. Post-treatment MRI revealed resolution of intracranial component.
Figure 1: (a–c) Magnetic resonance imaging (MRI) scan of orbit and brain (T1-weighted, axial and coronal sections, at the time of first symptom 12 years back) showing soft tissue lesions in bilateral orbits with moderate contrast enhancement; (d) clinical photograph at the current presentation, showing bilateral axial proptosis and complete ptosis in left eye; (e and f) contrast-enhanced CT (CECT) scan (coronal and axial scans), done at the time of current presentation showing bilateral orbital masses involving both intraconal and extraconal spaces causing expansion of bony orbit with globe indentation on the left side with bilateral proptosis. Optic nerves and extraocular muscles were not separately identifiable

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Currently, the patient presented with complaint of slowly progressive DOV OD of 15 days duration. On examination, visual acuity (VA) was 2/60 OD and PL (perception of light) negative OS. There was bilateral axial proptosis with mild limitation of EOM OD and complete external ophthalmoplegia OS [Figure 1]d. Fundus examination showed mild temporal disc pallor OD and primary optic atrophy OU. Color vision was diminished. Contrast-enhanced computed tomography (CECT) scan revealed bilateral orbital masses involving intraconal and extraconal spaces, causing orbital expansion and globe tenting OS [Figure 1]e and [Figure 1]f No intracranial extension was seen. MRI orbit revealed enlargement of the inferior and lateral rectiin right orbit [Figure 2]a,[Figure 2]b,[Figure 2]c. The mass in the left inferior and posterior intraconal orbit extended to the orbital apex where the optic nerve could not be seen separately. The lesion was significantly more hypointense on T2-weighted imaging on the left side [Figure 2]d. CECT scan of the chest and abdomen, serum ANCA, ANA, anti-ds DNA, and rheumatoid factor levels were normal. HPE of IB taken from the right orbit showed sclerotic tissue with hyalinized blood vessels and chronic inflammatory cells, mainly plasma cells [Figure 2]e and [Figure 2]f. On immunohistochemistry, plasma cells were positive for IgG4 (>25/HPF) [Figure 2]i. Serum electrophoresis revealed IgG4, IgG levels, and IgG4/IgG ratio of 24 mg/dl, 1473 mg/dl, and 16.36%, respectively. A diagnosis of probable IgG4ROD was made. Oral steroid was started at a dose of 1mg/kg/day. There was prompt clinical response; VA improved to 6/6 and EOM improved in the right eye after two weeks of treatment. Color vision remained diminished. The steroids were slowly tapered over the next five weeks.
Figure 2: (a and b) MRI scan (T2-weighted; axial and coronal sections showing extremely hypointense soft tissue lesions in bilateral orbits causing enlargement of inferior and lateral rectus muscles on right and obliteration of all the recti muscles and optic nerve on left side; (c and d) CECT scan (sagittal cut) and MRI (T2-weighted, axial cut) showing that optic nerve cannot be seen separately from the mass lesion; (e and f) histopathology showing sclerotic (collagenous) tissue with hyalinized blood vessels and chronic inflammatory cells, mainly plasma cells; (g–i) post-treatment CECT scan (axial, sagittal, and coronal cut) revealed significant resolution of right retrobulbar mass with reduction in extraocular muscle thickening such that optic nerve could be seen separately from the mass lesion

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Post-treatment CT scan revealed significant resolution of right retrobulbar mass with reduction in extraocular muscle thickening; optic nerve could now be seen separately from the lesion [Figure 2]g,[Figure 2]h,[Figure 2]i. During four years of follow-up, the patient has had no fresh complaints and his vision is stable.

  Discussion Top

Despite being an inflammatory pathology, clinical manifestations of IgG4ROD are mainly due to its mass effect, and usually there is no associated pain, redness, or edema.[2] The most common clinical manifestation reported in IgG4ROD is eyelid swelling followed by proptosis.[2–4] Umhera et al. published the comprehensive clinical diagnostic criteria for IgG4ROD.[5] The authors classified IgG4ROD as definite, probable, or possible, based on the presence of histological, clinical, and/or serological evidence. While definite disease requires all three evidences, the disease is labelled as probable if serology is normal, or possible if histology is not characteristic.[5] The present case had probable IgG4ROD; there was clinical and histological evidence but serum IgG4 levels were within normal limit (wnl).

A literature review for pIgG4ROD revealed a handful of cases [summarized in [Table 1]].[6–16] The current case, after initial manifestation in childhood, did not complain of any clinical progression for 12 years. However, a review of imaging showed a progression in disease extent.
Table 1: Previous cases of pediatric Ig4ROD reported in literature

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The patient presented to us with a recent onset DOV (OD), likely due to the involvement of the orbital apex. On imaging, the lesion was more hypointense in the left orbit compared to the right. This could be due to the difference in duration of the disease. The histopathological patterns described in IgG4 disease are classified as lymphomatous, mixed, and sclerotic.[17] It has been proposed that the histopathological pattern may be altered by the microstructure of the tissue and the age of the lesion.[11]

A review of literature showed that oral steroids were the most common first line treatment used for pIgG4ROD. The current case had a prompt response to oral steroids, both in clinical symptoms and imaging findings. There was a residual defect in color vision that can be explained by longstanding subclinical compression of the optic nerve, or insult sustained during the first episode. Intravenous pulse steroid, mycophenolate mofetil, cyclophosphamide, cyclosporine, methotrexate, and surgical debulking have also been used for treatment. Rituximab (anti-CD20 monoclonal antibody) has recently emerged as a promising treatment for compressive optic neuropathy caused by IgG4ROD.[17]

  Conclusion Top

To conclude, this case provides a rare insight into the natural course of pIgG4ROD and illustrates that pIgG4ROD may have a delayed diagnosis due to its clinically indolent nature. Early identification and treatment may control disease progression. All cases of pediatric IOI must be investigated to rule out IgG4ROD.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Stone JH, Zen Y, Deshpande V. IgG4-related disease. N Engl J Med 2012;366:539-51.  Back to cited text no. 1
Kubota T, Moritani S. Orbital IgG4-related disease: Clinical features and diagnosis. ISRN Rheumatol 2012;2012:412896. doi: 10.5402/2012/412896.  Back to cited text no. 2
Wallace ZS, Deshpande V, Stone JH. Ophthalmic manifestations of IgG4-related disease: Single-center experience and literature review. Semin Arthritis Rheum 2014;43:806-17.  Back to cited text no. 3
Deshpande V, Zen Y, Chan JK, Yi EE, Sato Y, Yoshino T, et al. Consensus statement on the pathology of IgG4-related disease. Mod Pathol 2012;25:1181-92.  Back to cited text no. 4
Umehara H, Okazaki K, Masaki Y, Kawano M, Yamamoto M, Saeki T, et al. Comprehensive diagnostic criteria for IgG4-related disease (IgG4-RD), 2012; Mod Rheumatol 22(1):21–30.  Back to cited text no. 5
Kalapesi FB, Garrott HM, Moldovan C, Williams M, Ramanan A, Herbert HM. IgG4 orbital inflammation in a 5-year-old childpresenting as an orbital mass. Orbit 2013;32:137-140.  Back to cited text no. 6
Griepentrog GJ, Vickers RW, Karesh JW, Azari AA, Albert DM, Bukat CN. A clinicopathologic case study of two patientswith pediatric orbital IgG4-related disease. Orbit 2013;32:389-91.  Back to cited text no. 7
Pasic S, Ristic G, Djuricic S. PReS-FINAL-2276: IgG4 re-lated disease in a 10-year-old girl. Pediatr Rheumatol 2013;11(Suppl 2):26621.  Back to cited text no. 8
Sane M, Chelnis J, Kozielski R, Fasiuddin A. Immunoglobulin G4-related sclerosing disease with orbital inflam-mation in a 12-year-old girl. J AAPOS 2013;17:548-50.  Back to cited text no. 9
Jariwala MP, Agarwal M, Mulay K, Sawhney S. IgG4-related orbital inflammation presenting as unilateral pseudotumor. Indian J Pediatr 2014;81:1108-10.  Back to cited text no. 10
Mittal R, Ganguly A, Rath S, Das B, Mishra A. IgG4-relatedorbital inflammation presenting as bilateral proptosis in a child. Eye (Lond) 2014;28:1264-6.  Back to cited text no. 11
Notz G, Intili A, Bilyk JR. IgG4-related dacryoadenitis in a13-year-old girl. Ophthal Plast Reconstr Surg 2014;30:e161-3.  Back to cited text no. 12
Prabhu SM, Yadav V, Irodi A, Mani S, Varghese AM. IgG4-related disease with sinonasal involvement: A case series. Indian J Radiol Imaging 2014;24:117-20.  Back to cited text no. 13
[PUBMED]  [Full text]  
Batu ED, Arici ZS, Orhan D, Kiratli H, Ozen S. Immunoglobulin G4-related orbital disease: Report of two pediatriccases. Clin Exp Rheumatol 2015;33:409-10.  Back to cited text no. 14
Gillispie MC, Thomas RD, Hennon TR. Successful treat-ment of IgG-4 related sclerosing disease with rituximab: A novelcase report. Clin Exp Rheumatol 2015;33:549-50.  Back to cited text no. 15
Jalaj S, Dunbar K, Campbell A, Kazim M. Treatment of pediatric IgG4-related orbital disease with TNF-alphaInhibitor. Ophthalmic Plast Reconstr Surg 2017;34:e10-2.  Back to cited text no. 16
Cheuk W, Yuen HK, Chan JK. Chronic sclerosing dacryoadenitis: Part of the spectrum of IgG4-related Sclerosing disease? Am J Surg Pathol 2007;31:643-5.  Back to cited text no. 17


  [Figure 1], [Figure 2]

  [Table 1]


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