Idiopathic Granulomatous Orbital Inflammation with Right Frontal Nerve Involvement: A Case Report Open Access

Idiopathic granulomatous orbital inflammation (IGOI) is regarded as a variant of non-specific orbital inflammation [1]. It is a diagnosis of exclusion, made in cases of an orbital mass composed histologically of granulomatous inflammation for which serological and radiological testing fails to show evidence of systemic sarcoidosis or any other cause [2]. The authors report a case of IGOI with frontal nerve involvement, which has not previously been reported. 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/10.1159/000535235).

A 75-year-old female presented with a 4-week history of right-sided scalp dysaesthesia and formication and a 2 week history of ipsilateral ptosis. On examination, visual acuity was 20/25 bilaterally with normal intraocular pressures. The ophthalmic examination did not reveal any evidence of uveitis. There was a palpable smooth painless mass in the right superior and inferior orbit, with associated right-sided proptosis of 4 mm and globe dystopia of 2 mm. There was almost complete right ptosis and no levator function. Extraocular motility was full, and optic nerve function was normal.

Investigations revealed an unremarkable inflammatory and vasculitic screen (including C-reactive protein, erythrocyte sedimentation rate, anti-nuclear antibody, proteinase 3, and myeloperoxidase antibodies). Angiotensin-converting enzyme (ACE) was normal at 52, and serum IgG4 was within normal limits. Magnetic resonance imaging (MRI) of the orbits was performed and confirmed a right supraorbital mass, the epicentre of which was located within the lacrimal gland with extension into the superior and lateral aspects of the orbit (Fig. 1). The mass showed homogenous enhancement and restricted diffusion suggestive of either a lymphoproliferative or inflammatory process. The frontal nerve was enlarged and enhancing.

An orbital biopsy via a superior lid crease approach was performed, which demonstrated non-caseating granulomatous inflammation with no acid-fast bacilli or fungal elements seen on staining. Areas of granulomatous inflammation contained tight collections of epithelioid histiocytes, without evidence of vasculitis. PCR testing for tuberculosis of the biopsy specimen was also negative. A computed tomography chest, abdomen, and pelvis scan showed no systemic disease.

A diagnosis of IGOI was thus made. An intralesional triamcinolone injection was given, delivered via a 25-gauge needle to the superior orbit, and the patient was additionally commenced on oral prednisolone 50 mg daily for 2 weeks followed by a taper, reducing the dose by 5 mg every fortnight until ceased to reduce the risk of recurrence. At subsequent review 8 weeks later, the right upper lid ptosis and palpable mass in the superior orbit remained. A repeat intralesional triamcinolone injection was given, and the patient was instructed to increase prednisolone to 25 mg daily with a plan to wean by 5 mg every fortnight.

Following cessation of steroid treatment, there was residual ptosis and superior orbital mass. Repeat MRI (Fig. 2) demonstrates a size reduction of the orbital mass. A right ptosis repair and repeat orbital biopsy were performed, which again showed non-caseating granulomatous inflammation most consistent with IGOI. At 14-month follow-up, a repeat ACE level was normal and there was no evidence of systemic sarcoidosis. Her orbital disease also remained stable. The patient will continue to undergo long-term follow-up to monitor development of sarcoidosis.

IGOI is a rare entity for which associated frontal nerve involvement has not been previously reported. As in the case described here, IGOI is a diagnosis of exclusion made when appropriate clinical examination, imaging, and biopsy have failed to definitively diagnose any other condition [3]. Important causes of granulomatous orbital inflammation include sarcoidosis, extrapulmonary tuberculosis, and granulomatosis with polyangiitis. In particular, it is difficult to differentiate IGOI from isolated orbital sarcoidosis. Sarcoidosis is characterised by the deposition of granulomas in various organs, of which 90% have pulmonary manifestation of the disease, most commonly seen as hilar lymphadenopathy [4]. Involvement of the eye is seen in approximately a quarter of sarcoidosis patients [5]. This most commonly manifests as uveitis, however, adnexal manifestations that may mimic isolated IGOI have been reported [5]. IGOI is thought to be more closely related to orbital pseudotumour than orbital sarcoidosis; however, the distinction remains unclear in the ophthalmic literature [6].

There are no universally accepted histological classification criteria that have been agreed upon. Sarcoidosis and IGOI usually display features of non-caseating granulomas [6, 7]. These lesions do not exhibit the same necrotic features of caseating granulomas and are often seen together with giant cells [7]. Conversely, IGOI is distinct from GPA and TB. GPA may be distinguished due to its characteristic vasculitic appearance, typically involving the adventitia and media of small vessels [5]. Tuberculotic lesions display features of a caseating granuloma, which manifests an appearance similar to necrosis with evidence of dead cells with no nuclei and cheese-like debris [6, 8]. Lesions caused by sarcoidosis may manifest as epithelioid granulomas characterised by a discrete collection of giant cells, lymphocytes, and epithelioid histiocytes [6]. The histological appearance of IGOI is less well defined. This may comprise a variable mix of multinucleated giant cells, histiocytes, and lymphocytes. Importantly, IGOI lacks the necrotizing appearance of other differential diagnoses [5].

Additionally, the unique aspect of this case was the frontal nerve involvement. Several causes of frontal nerve enlargement have been well-documented, including neoplastic perineural spread from squamous cell carcinoma, IgG4-related ophthalmic disease, and lymphoproliferative disorders. Perineural spread is a form of local neoplastic invasion in which tumour cells migrate along the nerve sheath, causing neural enlargement [9]. It often shows involvement of the trigeminal nerve and its branches [10]. IgG4-related ophthalmic disease can present with deposition of fibro-inflammatory lesions richly infiltrated with IgG4 plasma cells with frontal nerve and intracranial involvement [10]. Adult-onset xanthogranuloma associated with frontal nerve enlargement was recently reported [11]. In this case, there was widespread extraconal involvement including of the lacrimal gland, extraocular muscles, intracranial and pterygopalatine fossae as well as the frontal nerve [11]. Both enlargement and heterogenous enhancement of the frontal nerve on MRI were reported in this case [11]. There has been one documented case of imaging-confirmed nerve enlargement in a patient with sarcoidosis with involvement of the right tibial nerve [12]. To the authors’ knowledge, this is the first documented case of frontal nerve enlargement secondary to IGOI, which was consistent with the clinical findings of dysaesthesia.

Systemic corticosteroids comprise the first-line treatment for IGOI [13]. Intralesional triamcinolone injections followed by systemic corticosteroids were used to maximize the likelihood of symptom resolution in this case. Different regimens for intralesional corticosteroid injection exist for orbital inflammatory disease but varied between 5 mg and 40 mg of intralesional triamcinolone, for a total of 1–3 injections [14]. Recommended systemic corticosteroid regimens have begun at 1 mg/kg daily for 2 weeks followed by a slow taper over several months depending on treatment response [5, 15]. Despite the majority of patients responding well to corticosteroids, long-term screening for systemic sarcoidosis in IGOI is still required.

The diagnosis of IGOI is a rare entity representing a subtype of nonspecific orbital inflammation. The involvement of the frontal nerve was unique in this case and corresponded with neurological symptoms of dysaesthesia and formication. The primary differential diagnosis is orbital sarcoidosis, with other differentials including orbital neoplasm, GPA, and extrapulmonary tuberculosis. Treatment is most often a combination of intralesional and oral corticosteroids. Long-term monitoring is required to screen for systemic sarcoidosis.

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

The authors declare that there is no conflict of interest.

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

Dr. James Pietris completed the draft manuscript. Dr. Jessica Y. Tong and Prof. Dinesh Selva reviewed and edited the manuscript.

All data generated or analyzed during this study are included in this article and its online supplementary material. Further enquiries can be directed to the corresponding author.