IgG4-Related Ophthalmic Disease following COVID-19 Infection: Is it Associated or Incidental?

Introduction

IgG4-related disease (IgG4-RD) is a recently recognized immune-mediated fibroinflammatory disorder that presents as a tumor-like mass, forming lesions that have characteristic histopathological features with or without elevated serum IgG4 levels. It is a chronic disease that progresses with remissions and relapses, and it may cause sclerosis, destruction, and permanent organ failure unless treated properly and on time. Its definite etiology and triggering factors are still undetermined [1].

The most common organ manifestations involve the salivary glands, orbit, lymph nodes, pancreas, retroperitoneum, kidneys, and lungs. According to a large cohort, the orbit is the second most common manifestation area of IgG4-RD, and it is the first extra-pancreatic site reported in the literature [2]. When the disease emerges in the orbit, it is named IgG4-related ophthalmic disease (IgG4-ROD). The most commonly affected site in the orbit is the lacrimal gland. Extraocular muscles, trigeminal nerve, optic nerve, lacrimal duct system, and orbital soft tissue involvement have also been reported. The general presentation is a painless periorbital enlarging mass with erythema and proptosis [1].

The diagnostic criteria for IgG4-ROD are (1) an imaging test showing enlargement of the lacrimal gland, trigeminal nerve, or extraocular muscles as well as masses, enlargement, or hypertrophic lesions in various ophthalmic tissues; (2) a histopathological examination demonstrating lymphocytic and plasmacytic infiltration, IgG4+ plasmacytes are found and meet the following criteria: ratio of IgG4+ cells to IgG+ cells is 40% or above, or more than 50 IgG4+ cells per high-power field; and (3) a hematologic examination showing elevated serum IgG4 levels (above 135 mg/dL). The diagnosis is classified as “definitive” when all three criteria are met, “probable” when the first and second criteria are met, and “possible” when the first and third criteria are met [3].

IgG4-RD is one of the most frequently underdiagnosed diseases, since the histopathological and morphological properties are similar with other inflammatory conditions unless immunostaining is performed. Also, symptoms mimic a wide array of clinical conditions. Several study groups reexamined the biopsies of patients who were previously diagnosed with idiopathic orbital inflammatory disease and found that many of them were actually compatible with IgG4-ROD. The ratio of misdiagnosis was reported as between 16.7 – 33% in one review and 25 – 50% in another [4], [5].

For treatment, steroids are the first-line therapy regardless of organ involvement. Good initial therapeutic response to steroids is significant. In refractory and complicated diseases, conventional immunosuppressive/biological agents or surgery or radiotherapy are recommended [1].

Coronavirus disease 2019 (COVID-19) commonly presents with respiratory tract infections, but several reports documented ocular and orbital manifestations, including dry eye, conjunctivitis, keratitis, episcleritis, optic neuropathies, ocular cranial nerve palsies, orbital mucormycosis, retinopathies, retinal vasculopathies, and orbital inflammatory disease [6].

In this paper, we aimed to present a unique case of “definite” IgG4-ROD presenting as a large orbital mass in an adult following a recent COVID-19 infection.

Publication History

Received: 12 January 2023

Accepted: 22 May 2023

Article published online:
06 September 2023

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