Severe Panuveitis, Retinal Vasculitis, and Optic Disc Granuloma Secondary to Sarcoidosis

Abstract

Purpose

To report a case of panuveitis, retinal vasculitis, and optic disc granuloma due to sarcoidosis.

Methods

Case report and literature review.

Results

A 26 year-old previously healthy African American male presented with four months of gradual progressive visual decline in the right eye. Clinical examination revealed severe panuveitis, retinal vasculitis, and large optic nerve mass lesion. Diffuse supraclavicular lymphadenopathy was also present. Histopathologic examination of the lymph node biopsy revealed granulomatous inflammation with some areas of casseous necrosis, consistent with sarcoidosis.

Conclusion

Sarcoidosis is a common cause of uveitis and retinal vasculitis. In rare cases, an optic disc granuloma may occur and can be treated with immunosuppressive therapy.

Sarcoidosis is an idiopathic, multisystem granulomatous disorder with ocular involvement occurring in 25–60% of cases.¹ The histopathologic hallmark of the disease is noncaseating granuloma formation.^2,3 Clinically, optic nerve involvement can present as papilledema, papillitis, and/or granulomatous infiltration of the optic disc.^4,5 We report a case of sarcoidosis which presented with panuveitis, retinal vasculitis, and optic nerve granuloma.

Case Report

A 26 year-old previously healthy African-American male presented with four months of painless vision loss in the right eye. Review of systems was positive for floaters and progressive lymphadenopathy. Visual acuity was hand motions right eye and 20/25 left eye. A relative afferent pupillary defect was present in the right eye, and there was marked bilateral submandibular and supraclavicular lymphadenopathy. Slit lamp biomicroscopy of the right eye showed trace anterior segment inflammation and a large vascularized optic disc granuloma (Figure 1). There was also a peripapillary exudative retinal detachment, diffuse vascular sheathing, and a mid-peripheral choroidal granuloma. Ultrasonography revealed a 6.6 mm elevated optic nerve mass with low internal reflectivity. The left eye contained one focal area of vasculitis, and mild late disc leakage on fluorescein angiography.

Figure 1.

Montage fundus photograph of the right eye showing a very large vascularized optic disc granuloma with peripapillary exudative retinal detachment, and diffuse vasculitis. A mid-peripheral choroidal granuloma is visible in the inferotemporal quadrant.

The patient was admitted for further evaluation and lymph node biopsy. Angiotensin-converting enzyme and lysozyme levels were markedly elevated, while Quantiferon testing for tuberculosis was negative. Additional serologic testing for syphilis, human immunodeficiency virus, toxoplasmosis, and fungemia were negative. Chest computed tomography demonstrated bilateral hilar lymphadenopathy and diffuse nodular densities. Cervical lymph node biopsy revealed granulomatous inflammation with some areas of casseous necrosis (Figure 2). Acid-fast bacilli and gomori methenamine silver stains were negative for tuberculosis and fungus, respectively, and flow cytometry showed no immunophenotypic evidence of lymphoma.

Figure 2.

Histopathologic examination reveals granulomatous inflammation including palisading epithelioid histocytes (arrowhead) and giant cells (*) surrounding an area of casseous necrosis (arrow). (Hematoxalin-eosin, original magnification 10x)

The patient’s clinical presentation as well as radiographic and histopathologic examinations were consistent with advanced sarcoidosis and he was started on intravenous corticosteroids. He was transitioned to a slow oral prednisone taper, and because of the severity and extent of his disease, he was started on subcutaneous adalimumab therapy. There was significant improvement in the lymphadenopathy and subjective visual improvement within the first few weeks of treatment. At 21 months follow-up, his vision remained hand motions, but the optic nerve granuloma had decreased to 2.2 mm in thickness (Figure 3). The left eye remained 20/20 and showed no signs of clinical activity.

Figure 3.

Color fundus photograph of the right eye 21 months after presentation. The optic disc margins are partially visible and the granuloma is much smaller in size. There is extensive prepapillary and subretinal fibrosis and diffuse sclerosis of the retinal vessels.

Discussion

Sarcoidosis is most frequently a multisystem granulomatous disorder thought to result from an exaggerated immune response to a variety of antigens.¹ The exact pathogenesis remains unclear. The disease most often affects the lungs and thoracic lymph nodes, skin, and eyes, with anterior and posterior uveitis being the most frequent ocular manifestations.¹ The diagnosis remains one of exclusion and is based on clinical, radiographic, and histopathologic findings.¹ Radiographic testing typically reveals hilar lymphadenopathy and is often associated with elevated angiotensin-converting enzyme and lysozyme levels, all of which were present in our patient.¹

This patient’s lymph node biopsy revealed tightly formed granulomas with some areas of casseous necrosis. While noncaseating granulomas are the hallmark histopathologic finding in sarcoidosis, Mitchell and colleagues and others reported that minor degrees of caseous necrosis can still be compatible with the diagnosis.³ Although many of the clinical and histopathologic findings in sarcoidosis resemble those in patients with infectious diseases, no pathogenic organism has been implicated in its cause. In this case, our patient demonstrated negative serology and histopathology for syphilis, tuberculosis, toxoplasmosis, bartonella, cryptococcus, histoplasmosis and human immunodeficiency virus.

Table 1 illustrates the nine reported cases of optic disc granuloma secondary to sarcoidosis since 1980. Our patient was slightly younger than the average age of these patients, which was 35 years. Almost all patients were African American and all had unilateral optic disc granulomas. Our patient appears to have the largest granuloma of those reported. The presenting visual acuity varied among the patients with four eyes having ≥ 20/30 vision and four eyes having ≤ 20/200 vision. Oral and/or intravenous corticosteroids were the initial treatment of choice and visual outcomes were mixed.

Table 1.

Clinical characteristics and visual outcomes in patients with optic disc granuloma secondary to sarcoidosis since 1980.

Publication	Age/Sex (Years)	Race	Laterality of Granuloma	Initial VA	Treatment/Clinical Course	Length of Follow-up	VA at Last Follow-up
Lustgarten6	32/Female	African American	Unilateral (Left eye)	20/30	Vision declined over several weeks to 20/200, unresponsive to oral corticosteroids. Sudden vision loss to NLP several weeks later due to optic disc granuloma.	13 months	NLP
Graham7	43/Female	West Indian	Unilateral (Left eye)	NLP	Oral corticosteroids failed to improve vision	2 years	NLP
Farr5	31/Female	African American	Unilateral (Left eye)	20/25	2 months after presentation, vision declined to 20/400. Oral corticosteroids started with 6 month taper	18 months	20/25
Asensio Sanchez8	59/Male	Not reported	Unilateral (Left eye)	20/200	Oral corticosteroids started	1 year	20/20
Frohman9	50/Female	Not reported	Unilateral (Left eye)	NLP	Not reported	Not reported	Not reported
Frohman9	32/Female	Not reported	Unilateral (Left eye)	20/70	Not reported	Not reported	Not reported
Koczman10	24/Male	African American	Unilateral (Left eye)	20/25	Oral/IV corticosteroids and methotrexate	Not reported	20/15
Moschos11	19/Male	African American	Unilateral (Left eye)	20/25	Not reported	Not reported	Not reported
Current Study	26/Male	African American	Unilateral (Right eye)	HM	IV corticosteroids followed by slow oral corticosteroid taper and adalimumab	22 months	HM

HM: Hand motions; IV: Intravenous; NLP: No light perception; VA: Visual acuity

The list of differential diagnoses for a mass lesion on or around the optic nerve head in the setting of uveitis is relatively broad. Neoplastic, inflammatory, and vascular lesions are among the most common etiologies. Specific diseases include peripapillary choroidal hemangiomas or metastasis, amelanotic choroidal melanomas, sarcoid or tuberculous granulomas, and possibly Blau syndrome. Blau syndrome is a rare, autosomal dominant condition typically characterized by early-onset granulomatous arthritis, uveitis and skin lesions.¹² While optic disc granulomas have not been specifically described in this condition, the granulomatous uveitis can be severe and multifocal choroiditis has been reported.¹²

Central nervous system involvement has been estimated to occur in 5–12% of all cases of sarcoidosis.¹³ Optic neuritis, myelopathy, and facial nerve palsy are among the most common presentations of those with neurosarcoidosis.¹³ The prognosis is variable but particularly poor when the optic nerve is involved.¹³ The development of an optic disc granuloma is exceedingly rare. Farr reported a case of acute vision loss secondary to a sarcoid optic disc granuloma and good visual recovery with oral corticosteroid use.⁵ Our patient responded to immunosuppressive therapy but suffered significant vision loss because of the severity and chronicity of disease at presentation.

Summary Statement.

The patient presented with profound painless vision loss in the right eye and was found to have severe panuveitis, retinal vasculitis and optic disc granuloma due to sarcoidosis. The disease was managed with immunosuppressive therapy consisting of corticosteroids and adalimumab.