• Users Online: 917
  • Print this page
  • Email this page

 Table of Contents  
Year : 2022  |  Volume : 2  |  Issue : 2  |  Page : 419-421

Possible IgG4-related disease in a case of necrotizing scleritis

1 Senior Resident, Giridhar Eye Institute, Ernakulam, Kerala, India
2 Department of Orbit, Oculoplasty and Ocular Oncology, Giridhar Eye Institute, Ernakulam, Kerala, India
3 Department of Cornea and Refractive Surgery Services, Giridhar Eye Institute, Ernakulam, Kerala, India
4 Department of Vitreoretina, Giridhar Eye Institute, Ernakulam, Kerala, India
5 Ocular Pathology, Sankara Nethralaya, Chennai, India
6 Department of Rheumatology, Centre For Arthritis And Rheumatism Excellence (CARE), Nettoor, Cochin, India

Date of Submission28-May-2021
Date of Acceptance10-Jan-2022
Date of Web Publication13-Apr-2022

Correspondence Address:
Marian Pauly
Department of Orbit, Oculoplasty and Ocular Oncology, Giridhar Eye Institute, Kochi, Kerala - 682 020
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijo.IJO_1455_21

Rights and Permissions

Necrotizing scleritis can be a diagnostic and therapeutic challenge. We present a case of a 51-year-old female, who had necrotizing scleritis treated for 9 years with intermittent corticosteroid therapy. In view of its recalcitrant nature, she underwent scleral biopsy, which revealed histopathological features suggestive of IgG4- related disease. This case report highlights the importance of including IgG4-related disease as a differential diagnosis of scleritis and the role of scleral biopsy as a diagnostic tool in unresponsive cases.

Keywords: Histopathology, IgG4-related disease, scleral biopsy, scleritis

How to cite this article:
Giridhar D, Pauly M, Pillai VS, Anantharaman G, Subramanian K, Shenoy P, Vijayan A. Possible IgG4-related disease in a case of necrotizing scleritis. Indian J Ophthalmol Case Rep 2022;2:419-21

How to cite this URL:
Giridhar D, Pauly M, Pillai VS, Anantharaman G, Subramanian K, Shenoy P, Vijayan A. Possible IgG4-related disease in a case of necrotizing scleritis. Indian J Ophthalmol Case Rep [serial online] 2022 [cited 2022 May 27];2:419-21. Available from: https://www.ijoreports.in/text.asp?2022/2/2/419/342886

IgG4-related disease (IgG4-RD) is a systemic immune-mediated condition characterized by tissue infiltration with lymphocytes and IgG4-secreting plasma cells.[1] The most frequent systemic manifestations include Type I autoimmune pancreatitis and salivary gland involvement.[1] The frequency of ophthalmic involvement ranges from 4 to 34% of IgG4-RD patients.[2] Lacrimal gland is the most common site of ophthalmic involvement.[2] We report an isolated case of necrotizing scleritis in whom the histopathology was suggestive of IgG4-related disease.

  Case Report Top

A 51-year-old female presented with complaints of recurrent attacks of ocular pain and redness in the left eye for 9 years. She was a diabetic on oral hypoglycemic agents since 9 years. She has been treated with oral steroids and antituberculosis treatment in the past. However, she continued to have recurrent episodes of pain in the left eye and hence came for further management.

On examination, the best-corrected visual acuity (BCVA) was 6/7.5, N6 in the right eye and CF 3 m, and N36 in the left eye. Anterior segment of the left eye revealed inflammation of the temporal bulbar conjunctiva, anterior chamber cells, and diffuse swelling of the temporal sclera with areas of necrosis [Figure 1]a and [Figure 1]b. Fundus examination revealed vitritis and exudative retinal detachment [Figure 1]c. Examination of the right eye was normal. She was diagnosed with necrotizing scleritis in the left eye. Her erythrocyte sedimentation rate was 25 mm/h. Serum angiotensin-converting enzyme, antinuclear antibody, rheumatoid factor, and antineutrophil cytoplasmic antibodies were normal. Considering inadequate response to systemic corticosteroids, she underwent scleral biopsy from the affected area (4 × 2 × 2 mm specimen) including a portion of adjacent normal sclera. Histopathology revealed dense infiltrates of lymphocytes and plasma cells with perivascular arrangement of lymphoplasmacytic cells suggestive of IgG4-related disease [Figure 1]d. She was referred to the rheumatologist and started on pulse methylprednisolone (500 mg) for 3 days and initiated on azathioprine with oral steroids (0.5 g/kg). As she developed proximal myopathy with steroids, she was switched to rituximab (500 g, 2 weekly interval). Oral steroids were tapered and stopped, and she was maintained on azathioprine (2 mg/kg).
Figure 1: Clinical picture of the patient diagnosed as necrotizing scleritis. (a and b) inflammation of the temporal bulbar conjunctiva associated with the areas of scleral necrosis. (c) Fundus photo showing hyperaemia of the optic disc and loss of normal retinal transparency. (d) Histopathology: Haematoxylin-eosin stain showing perivascular arrangement of lymphoplasmacytic cells

Click here to view

At 3-month follow up, BCVA in the left eye improved to 6/12, N12. The scleral inflammation had reduced and exudative retinal detachment resolved.

At 1-year follow up, BCVA reduced to 6/18, N18 due to posterior subcapsular cataract. Fundus was normal. Sclera remained quiet, but thinning progressed to perforation. She underwent corneoscleral patch graft under cover of rituximab. Intraoperatively, scleral thinning with prolapsed uveal tissue was noted measuring 5 × 4 mm over the temporal sclera [Figure 2]a and [Figure 2]b. Corneoscleral graft of the required dimension was trephined and placed over the area of thinning and sutured to the adjacent sclera with 10-0 nylon. Postoperatively, the graft has taken well with no recurrence of inflammation [Figure 2]d. She is on maintenance therapy with azathioprine.
Figure 2: Clinical picture on 1-year follow-up shows. (a and b) scleral thinning with uveal show. (c) Fluorescein stain over the area of scleral thinning examined under a blue filter showing positive Seidel's test. (d) postoperative clinical picture after scleral patch graft

Click here to view

  Discussion Top

IgG4-RD is a multiorgan disease characterized by tumefactive lesions with dense lymphoplasmacyctic infiltration, rich in IgG4 positive plasma cells, fibrosis, and in some organs, an obliterative phlebitis. In the orbit, it commonly affects the lacrimal gland, but can also affect structures like extraocular muscles, orbital fat, eyelid, and infraorbital and supraorbital nerves.[2] The signs and symptoms of ocular disease may be chronic lid swelling or proptosis with mild or no signs of inflammation.[2] Even though diffuse and nodular scleritis[3],[4],[5],[6] have been reported with IgG4-RD, necrotizing scleritis has rarely been reported. IgG4-RD involving the sclera has been misdiagnosed as intraocular tumor or choroidal tumor, which led to enucleation of the eyeball.[7] Inadequate response to steroid treatment in a case of scleritis should prompt the clinician to perform further investigations.

The diagnostic criteria for IgG4-RD include two or more of the following: (1) characteristic diffuse/localized swelling or masses in single or multiple organs, (2) hematologic examination shows elevated serum IgG4 concentrations (≥135 mg/dL), and (3) histopathologic examination shows: marked lymphocyte and plasmacyte infiltration and fibrosis, infiltration of IgG4+ plasma cells: ratio of IgG4+ to IgG+ cells >40% and >10 IgG4+ plasma cells/HPF.[8] Serum IgG4 levels can be normal in approximately 30% of patients. In our case, the patient had single organ involvement, normal serum IgG4 levels, and histopathological features suggesting IgG4-related disease, thus satisfying two of the above criteria, and hence, we consider it as a case of possible IgG4-related disease.[8] Philippakis et al.[3] reported a case of nodular scleritis diagnosed after 13 years of onset and developed pulmonary involvement at the time of diagnosis. Kim et al.[6] reported a case but had orbital and lung involvement at the time of diagnosis. Attiku et al.[5] reported intraocular IgG4 disease masqueraded as nodular scleritis diagnosed after surgical excision. In our case, it was necrotizing scleritis with vitritis and exudative retinal detachment. Although histopathology showed lymphoplasmacytic infiltrate, it did not satisfy the immunohistochemistry criteria. The small sample as well as necrotizing pathology and frequent treatment with steroids might have altered the pathology as the disease was partly responding to systemic steroids. We also assume that frequent systemic steroids prevented the onset of systemic involvement.

Systemic corticosteroids are the first line therapy for the treatment of IgG4-related ocular disease. Initial response to steroids is good, but relapse rates have been reported either during treatment or after cessation of steroid use.[9] In case of relapses, immunosuppressive agents like methotrexate and azathioprine have a crucial role.[9] Rituximab is said to be 90% effective in cases of relapse.[10] Our patient was started on rituximab therapy and showed significant symptomatic and clinical improvement.

  Conclusion Top

IgG4-RD presenting as isolated scleritis is a rare entity and may be considered in the differential diagnosis of scleritis. Scleral biopsy in such cases can help to confirm diagnosis and start appropriate management.

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

McNab AA, McKelvie P. IgG4-related ophthalmic disease. Part I: Background and pathology. Ophthalmic Plast Reconstr Surg 2015;31:83-8.  Back to cited text no. 1
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. 2
Philippakis E, Cassoux N, Charlotte F, LeHoang P, Bodaghi B, Bloch-Queyrat C, et al. IgG4-related disease masquerading as recurrent scleritis and chronic conjunctivitis. Ocul Immunol Inflamm 2015;23:168-72.  Back to cited text no. 3
Berkowitz E, Arnon E, Yaakobi A, Cohen Y, Tiosano B. IgG4-related disease presenting as isolated scleritis. Case Rep Ophthalmol Med 2017;2017:4876587.  Back to cited text no. 4
Attiku Y, Rishi P, Biswas J, Krishnakumar S. Intraocular IgG4 disease masquerading as nodular scleritis. Indian J Ophthalmol 2020;68:1935-6.  Back to cited text no. 5
[PUBMED]  [Full text]  
Kim SJ, Lee SU, Kang MS, Ahn JH, Shin J, Park CY, et al. IgG4-related disease presenting as recurrent scleritis combined with optic neuropathy. BMC Ophthalmol 2021;21:5.  Back to cited text no. 6
Ohno K, Sato Y, Ohshima K, Takata K, Ando M, Abd Al-Kader L, et al. IgG4-related disease involving the sclera. Mod Rheumatol 2014;24:195-8.  Back to cited text no. 7
Umehara H, Okazaki K, Masaki Y. Comprehensive diagnostic criteria for IgG4-related disease (IgG4-RD), 2011. Mod Rheumatol 2012;22:21-30.  Back to cited text no. 8
Detiger SE, Karim AF, Verdijk RM, van Hagen PM, van Laar JAM, Paridaens D. The treatment outcomes in IgG4-related orbital disease: A systematic review of the literature. Acta Ophthalmol 2019;97:451-9.  Back to cited text no. 9
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.  Back to cited text no. 10


  [Figure 1], [Figure 2]


Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

  In this article
Case Report
Article Figures

 Article Access Statistics
    PDF Downloaded30    
    Comments [Add]    

Recommend this journal