Case Report: A Peculiar Pinguecula? A Surprising IgG4-Related Conjunctival Lesion

Abstract

Introduction

IgG4-related disease (IgG4-RD) is a chronic immune-mediated fibroinflammatory condition that may involve multiple organs but rarely presents as an isolated conjunctival lesion. Ocular surface involvement can mimic benign inflammatory conditions, leading to diagnostic delay. We report a rare case of isolated conjunctival IgG4-RD initially misdiagnosed as recurrent pingueculitis.

Case Presentation

A 37-year-old female presented with a gelatinous, cystic mass on the bulbar conjunctiva. Comprehensive ophthalmic examination and anterior segment optical coherence tomography (OCT) revealed a well-demarcated subconjunctival lesion without scleral or intraocular invasion. Differential diagnoses included conjunctival lymphoma, ocular surface squamous neoplasia, and nonspecific orbital inflammation. An excisional biopsy was performed, and histopathological examination confirmed IgG4-RD, demonstrating dense lymphoplasmacytic infiltration with CD138- and IgG4-positive plasma cells, storiform fibrosis, and abundant collagen fibers. Postoperatively, a suspected local recurrence was successfully treated with topical dexamethasone. At 6-month follow-up, complete clinical remission was achieved without additional local or systemic therapy.

Conclusion

This case highlights the importance of considering IgG4-RD in the differential diagnosis of atypical conjunctival lesions. Tissue biopsy remains essential for definitive diagnosis, while adjunctive imaging modalities such as anterior-segment OCT may aid in lesion characterization, even in the absence of systemic disease.

Introduction

IgG4-related disease (Ig4-RD) is now a well-established systemic disease. It is a multi-organ, fibro-inflammatory condition, in which any organ can be involved, but the most commonly involved organs are the pancreas, kidneys, lymph nodes, orbital adnexal structures, salivary glands, and retroperitoneum [1]. The diagnosis of the disease is made with pathological examination that demonstrates plasma cells infiltrate with IgG4-positive staining, storiform fibrosis, obliterative phlebitis, and a variable number of eosinophils. The pathology is very specific and looks similar in all organs [2]. Regarding the orbital and ocular involvement, the lacrimal gland is the most commonly involved organ in IgG4-RD (62–88%) [3–5]. Other ocular involvement includes the trigeminal nerve, extraocular muscles, orbital fat, eyelid, and the nasolacrimal duct system. There are cases that demonstrated conjunctival involvement, but this is only in rare cases [6–9]. Prognosis is known to be quite well, while some patients have spontaneous resolution [10]. Treatment with glucocorticoids is well established; initial response to systemic corticosteroids is excellent (89–100%), but relapse rates have been reported as high as 70% either during or after treatment [11]. In this case, we would like to present a conjunctival lesion as the presenting sign of IgG4-RD.

Case Report

A 37-year-old female is presented to cornea clinic at Meir medical center due to a diagnosis of recurrent pinguiculitis and multiple flair ups after topical corticosteroid cessation. She was treated for inflamed pinguecula on her left eye with topical dexamethasone phosphate 0.1% intermittently for 6 months. When arriving to the clinic, a thorough history reveals photorefractive keratectomy to correct myopia 15 years ago on both eyes and no previous ocular trauma or contact lens use. Systemic history includes fertility treatment and no chronic illness and no relevant family history. On presentation, her visual acuity was 20/20 in both eyes with no correction. Ophthalmic examination was normal with the exception of a gelatinous, cystic mass measuring 4 × 4 mm with no feeding vessel located nasally on the bulbar conjunctiva of the left eye (Fig. 1). Intraocular pressure was 12 mm Hg in both eyes. On the same visit, an anterior segment optical coherence tomography (OCT) was performed (Fig. 2). On the scan, a subconjunctival lesion with reflectivity similar to the conjunctiva was demonstrated with no acoustic shadow, no septations, and no invasion to inner structures. The differential diagnosis included lymphoma, squamous neoplasia, nonspecific orbital inflammation, and pingueculitis. Due to high suspicion for neoplasia and the unsatisfying resolution with topical treatment, an excisional biopsy with 3 mm margin was performed, using mitomycin C 0.02% and cryoablation around the margins. No sutures were needed as the end result was bare sclera.

Fig. 1.

Eye at presentation: a noticeable gelatinous, cystic mass measuring 4 × 4 mm with no feeding vessel located nasally on the bulbar conjunctiva of the left eye.

Fig. 2.

Lesion biopsy on the left side. Subconjunctival lesion was infiltrated with plasmatic cells positive for CD138 stains with no monoclonality. Staining for IgG4 was positive and 65 cells per high power field were observed. The IgG4:IgG ratio was 20%; storiform fibrosis and abundant collagen fibers also were demonstrated. On the left side, AS-OCT image demonstrating the subconjunctival lesion with reflectivity similar to the conjunctiva with no acoustic shadow, no septations, and no invasion to inner structures.

On the biopsy (Fig. 2), the subconjunctival lesion extracted was infiltrated with plasmatic cells positive for CD138 stains with no monoclonality. Staining for IgG4 was positive and 65 cells per high power field were observed. The IgG4:IgG ratio was 20% (Fig. 2). Storiform fibrosis and abundant collagen fibers also were demonstrated. Based on the clinical examination and pathology report, the patient was diagnosed with conjunctival inflammation suggestive of IgG4-RD. The post-surgical regimen of treatment was topical dexamethasone phosphate 0.1% for 4 times a day with slow tapering, moxifloxacin hydrochloride 0.5% for 4 times a day for 1 week, and cyclopentolate hydrochloride 0.1%, 2 times a day for 1 week. We continued to follow the patient for another 6 months in which at one visit, 3 months post-surgery a recurrence was suspected with mild subjective irritation and a small injected area with no apparent nodule on the nasal bulbar conjunctiva. A course of topical dexamethasone 3 times per day with a month of tapering down was successful and by 6 months there was a complete resolution, after 2 months with no treatment (Fig. 3).

Fig. 3.

Eye 2 months post-surgery with no current treatment. The lesion is not clinically visible or disturbing.

Discussion

Our case demonstrates a very rare case of an isolated IgG4-related conjunctival lesion with no other ocular or systemic involvement. The clinical presentation of an unknown, evolving bulge on the sclera and conjunctiva encompasses a broad differential diagnosis. Certain characteristics may raise suspicion for malignancies, while others suggest an inflammatory etiology. Additionally, some presentations may be mistakenly attributed to degenerative conditions such as pterygium or pinguecula, leading to potential oversight in diagnosis. It is well established that the diagnosis should be made with biopsy, but we wanted to emphasize the use of anterior-segment OCT as part of the diagnostic and follow-up procedure. While examining the patient, we could have a better understanding of the lesion properties by using the anterior-segment OCT, discovering its level of invasion, the inner reflectivity, lack of inner cyst that might have suggested a melanocytic origin, no hyper-reflectivity that characterized pterygium or pinguecula [12], and no abrupt transition between neoplastic epithelial lesion and normal epithelium that might have suggested OSSN [13]. The use of OCT did not make the biopsy futile, but it gave us a better understanding of the characteristics of the lesion prior to performing the biopsy and made the procedure safer with higher predictability. Regarding the patient findings, there are not many cases that report isolated conjunctival lesions with the diagnosis of IgG4-RD [7, 9]. In order to achieve the full diagnostic criteria of IgG4-RD, there should be a clinical inflammation lesion, elevated IgG4 levels on a biopsy, and high IgG4 levels in blood tests [14]. But serum IgG4 levels can be normal in up to 40% of patients with IgG4-RD [15]. Our patient, due to religious reasons, was not interested in completing the full systemic workup in the next year of follow-up. She completed a full gastroenterology exam that was normal and is clinically healthy, with no other complains. In a year of follow-up with no treatment and no relapse of the disease, we declared complete remission. In summary, the manifestations of IgG4-related ophthalmic disease present considerable variability, with a significant proportion of patients exhibiting orbital inflammatory reactive diseases. The underlying pathogenesis remains complex and not yet fully elucidated. Tissue biopsy combined with immunohistochemical staining serves as reliable examination methods for diagnosis. The application of glucocorticoids and immunosuppressants has demonstrated beneficial therapeutic effects; however, further large-sample statistical analysis is essential to establish a clinically guiding treatment protocol. Additionally, it is noteworthy that some patients may present atypically, necessitating a high level of suspicion in clinical assessment to ensure early and accurate diagnosis. In addition, the CARE Checklist has been completed by the authors for this case report, attached as online supplementary material (for all online suppl. material, see https://doi.org/10.1159/000551674).

Statement of Ethics

Ethical approval is not required for this study in accordance with local or national guidelines. Written informed consent was obtained from the patient for publication of the details of their medical case and any accompanying images.

Conflict of Interest Statement

The authors have no conflicts of interest to declare.

Funding Sources

This study was not supported by any sponsor or funder.

Author Contributions

Naama Lippin contributed to the conception and design of the work, acquisition and curation of data, writing of the manuscript, and project administration. Carol L. Karp contributed to supervision of the project, writing and critical revision of the manuscript, and validation of the data and conclusions. Asaf Friehmann contributed to the acquisition and curation of data and to writing and critical revision of the manuscript. All authors provided critical feedback and approved the final manuscript.

Funding Statement

This study was not supported by any sponsor or funder.

Data Availability Statement

The data that support the findings of this study are not publicly available due to patient privacy and confidentiality agreements but are available from the corresponding author upon reasonable request.