IgG4-related orbital disease presenting as optic... : Indian Journal of Ophthalmology - Case Reports (2024)

Immunoglobulin G4 (IgG4)-related disease is an autoimmune condition characterized by IgG4-positive plasma cell infiltration and elevated serum IgG4 concentrations. It is described in various organ systems, including the pancreas, kidney, biliary tree, salivary glands, and nervous system. Middle-aged and elderly males are commonly affected. Orbital involvement with mass lesions has been reported but optic neuropathy can also occur in IgG4-related disease, which is a rare presentation, and very few cases have been reported.

Case History

A 74-year-old male presented to us with a sudden diminution of vision in the left eye for 5 days. His visual acuity in the right eye was 6/6, N6 and in the left eye was counting finger 1 m, N36. Pupillary examination showed a relative afferent pupillary defect (RAPD) in the left eye. He was pseudophakic in both eyes. Fundus examination in the right eye showed a small optic disc, whereas the left eye fundus examination showed a hyperaemic optic disc. Ocular movements were full in both eyes. We advised blood tests to rule out systemic risk factors, and uncontrolled diabetes mellitus was reported (random blood sugar 300 mg/dl). Considering the possibility of anterior ischemic optic neuropathy, the patient was referred to the physician for urgent control of diabetes mellitus, and magnetic resonance imaging (MRI) of the brain with orbital cuts was advised to rule out neurological causes. Unfortunately, the patient was lost to follow-up and came back 2 months later with complete ptosis and proptosis in the left eye. All ocular movements were limited in the left eye [Fig. 1]. Visual acuity in the left eye dropped to the perception of light with an inaccurate projection of rays. There was persistent RAPD in the left eye. Left eye fundus examination showed a combined central retinal artery and central retinal vein occlusion with a cherry red spot [Fig. 2a]. Right eye examination as stated before was normal. Clinical diagnosis of orbital inflammation suggestive of orbital apex syndrome was made, which was confirmatory in MRI [Fig. 2c]. Key features in MRI were left proptosis, pachymeningitis, and a lesion encasing the intraconal optic nerve [Fig. 2d]. The patient was given three doses of intravenous pulse methylprednisolone (1 g/day) for 3 days followed by oral steroids (one mg/kg body weight) in weekly tapering doses. Still patient had minimal improvement, so a workup for infective/inflammatory/metastatic causes was done, and raised serum IgG4 was noted (more than 3.56 g/l). An incisional biopsy through lateral orbitotomy was done. Biopsy was taken from the mass in the lateral orbital wall and lateral rectus muscle. Histopathology showed moderate to dense interstitial lymphoplasmacytic infiltration and storiform fibrosis [Fig. 3a-d]. Immunohistochemistry was done in which the number of IgG-positive cells was 164/HPF [Fig. 3e] and the number of IgG4-positive cells was 108/HPF [Fig. 3f]. Currently, the patient is on mycophenolate mofetil 500 mg and is under follow-up. On one-year follow-up, visual acuity is unchanged, but there is a significant improvement in proptosis, ptosis, and ocular movements [Fig. 4]. Fundus examination of the left eye showed optic atrophy [Fig. 2b].

Discussion

IgG4-related disease has been associated with disease involvement in nearly every organ system. First identified in 1961^[1] as autoimmune pancreatitis, with large numbers of IgG4-positive cells, it was only in 2003 that Kamisawa et al.^[2] reported extrapancreatic lesions in patients with autoimmune pancreatitis containing histopathology identical to that found in the pancreas. Although there are reports of involvement of a variety of orbital structures in IgG4-related diseases like lacrimal gland, extraocular muscles, and trigeminal nerve as mass lesions, optic nerve involvement is rare.

The comprehensive clinical diagnostic criteria^[3] includes:

1. Clinical examination showing characteristic diffuse or localized swelling or masses in single or multiple organs
2. Elevated serum IgG4 concentration >135 mg/dl
3. Histopathologic examination showing marked lymphocytic and plasmacytic infiltration and storiform fibrosis.

Combination 1+2+3 = Definite IgG4 RD.

1+3 = Probable IgG4 RD.

1+2 = Possible IgG4 RD.

The most common neurological involvement in IgG4-related disease is fibroinflammatory thickening of the dura mater called pachymeningitis. Jing Li et al.^[4] investigated the involvement of optic neuropathy in IgG4-related disease based on MRI data and concluded that inflammation of optic nerve sheath and hypertrophic pachymeningitis are common causes of optic nerve injury.

Our patient initially presented clinically with all features suggestive of optic neuropathy. He had a clinical deterioration with drastic visual loss due to orbital apex syndrome possibly secondary to an immune-mediated inflammatory process. Tuberculosis, sarcoidosis, Wegener granulomatosis, or meningioma were considered in differential diagnosis.

Ohno et al.^[5,6] misdiagnosed two IgG4-related diseases as choroidal tumors and enucleation of the eyeball was performed. Our patient had the opportunity to avoid the discouraging surgery by simply performing serological tests.

Hamaoka et al.^[7] also reported a case series of 56 consecutive patients with a “definite case” of IgG4-related disease of whom seven patients presented with mass lesions around the optic nerve head in MRI and four patients showed symptoms of optic neuropathy. Hence attention should be paid to locations of orbital lesions and visual functions in these patients, especially in cases presenting with high serum IgG4 levels.

Gogineni et al.^[8] reported a case of a young 18-year-old boy who presented with bilateral optic neuropathy and bilateral hippocampal bleed-related neurological involvement diagnosed to have possible IgG4-related disease. They concluded that early diagnosis and treatment with systemic steroids can decrease the morbidity and mortality in such patients.

Establishing a diagnosis is important in planning immunosuppressive therapy and preventing future complications in IgG4-related disease. The initial outcome is favorable with high-dose corticosteroids but additional immunosuppressive agents may be required if the response is not sustained. IgG4-related disease presenting as optic neuropathy is rare and can be an early manifestation of orbital involvement. There are only a few reports documenting optic nerve involvement in IgG4-related disease [Table 1].

Early diagnosis and treatment of this rare entity improve the quality of life in these patients. A high index of suspicion, timely imaging, and close follow-up are essential for preventing permanent visual damage.

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: Nil.

Conflicts of interest: There are no conflicts of interest.

References