Slitlamp and fundus photographs. A, Slitlamp photograph demonstrates the large perilimbal subconjunctival nodule and fine keratic precipitates. B, Fundus photograph shows hazy media and yellowish subretinal exudates in the inferonasal quadrant. C, Slitlamp photograph 1 month following resection with scleral patch grafting. D, Significant tumor growth had occurred 1 year following resection.
Histopathologic examination. A, Histopathologic examination under low-power magnification demonstrates an infiltration of histiocytes and lymphocytes (hematoxylin-eosin, original magnification ×25). B, Proliferating histiocytes are present with abundant clear cytoplasm (hematoxylin-eosin, original magnification ×100). C, Immunohistochemical staining for S-100 protein was positive. Note the cluster of histiocytes demonstrating emperipolesis (arrow), which is diagnostic for Rosai-Dorfman disease (peroxidase-antiperoxidase, original magnification ×100).
Payne JF, Srivastava SK, Wells JR, Grossniklaus HE. Rosai-Dorfman Disease Simulating Nodular Scleritis and Panuveitis. Arch Ophthalmol. 2011;129(4):512-526. doi:10.1001/archophthalmol.2011.56
Scleritis is a potentially sight-threatening inflammatory condition of the sclera that may be associated with keratitis, uveitis, glaucoma, and exudative retinal detachments.1 Sinus histiocytosis with massive lymphadenopathy, or Rosai-Dorfman disease, is a rare histiocytic disorder characterized by massive, painless lymphadenopathy.2,3 While extranodal involvement is common, eye involvement is infrequent and most often seen in the orbit or eyelid.4 Direct ocular involvement is exceedingly rare.4 We report a case of Rosai-Dorfman disease that simulated nodular scleritis and panuveitis.
A 20-year-old woman with diabetes, hypertension, and hypothyroidism had a 3-day history of severe pain and vision loss in the left eye. She also noticed a slowly enlarging nodule on the left eye over the previous 5 months. Review of systems was negative for fever. Visual acuity was 20/20 OD and counting fingers OS. Intraocular pressure was 43 mm Hg OS. Examination showed an elevated perilimbal subconjunctival nodule, large keratic precipitates, 3+ anterior segment inflammation, 2+ vitreous haze, and subretinal exudate (Figure 1A and B). Ultrasonography revealed diffuse scleral thickening. Laboratory testing revealed no leukocytosis, a normal angiotensin-converting enzyme level, a nonreactive rapid plasma reagin test result, and a slightly elevated erythrocyte sedimentation rate (25 mm/h). Tuberculosis skin testing and chest radiography results were normal. Results of testing for antinuclear antibodies, anticytoplasmic nuclear antibodies, and HLA-B27 were negative.
She was diagnosed as having nonnecrotizing nodular scleritis with panuveitis and was treated with oral prednisone, topical prednisolone acetate, and topical antihypertensive eyedrops. She experienced frequent relapses over the following 6 months and began treatment with oral methotrexate. She was lost to follow-up for 4 years. During this time, a systemic evaluation for pelvic pain revealed a large mass, which was partially resected. Histopathologic examination showed histiocytic infiltration. She returned to the eye clinic with recurrent left eye pain and vision loss. She was restarted on a course of oral prednisone and subsequently underwent 2 subconjunctival injections of triamcinolone acetonide. Her ocular inflammation subsided and remained inactive for 3 years, but her vision was ultimately limited by a mature cataract. Progressive enlargement of the mass eventually led to severe globe displacement and an inability to close her eyelids.
Partial resection of the epibulbar mass was performed with scleral patch grafting (Figure 1C). Histopathologic examination showed histiocytes exhibiting emperipolesis and S-100 protein positivity (Figure 2), which are diagnostic for Rosai-Dorfman disease. At last follow-up, 1 year after resection, significant tumor regrowth had occurred (Figure 1D).
Rosai-Dorfman disease is a rare, idiopathic, benign proliferative histiocytic disorder originally described in 1969.5 It is most common in children and adolescents and is typically characterized by massive cervical lymphadenopathy, fevers, leukocytosis, and elevated erythrocyte sedimentation rate.2,3 Our patient was atypical in that she lacked cervical lymphadenopathy and leukocytosis and denied having fevers. Ocular involvement, which may be the initial and only manifestation of the disease, is atypical and seen in only 11% of patients.2,3 To our knowledge, there are only 2 other reported cases of Rosai-Dorfman disease with subconjunctival nodules and uveitis.4,6
Rosai-Dorfman disease can be difficult to diagnose and often requires histopathologic examination. Characteristic histology includes a polymorphous infiltrate with a predominance of proliferating histiocytes.2 The histiocytes usually contain prominent vesicular nucleoli and abundant pale, eosinophilic cytoplasm and exhibit lymphophagocytosis or emperipolesis.2 Immunocytological analysis will show positive staining for S-100 protein.4
Prognosis is generally good and usually self-limited. Typically, eventual spontaneous regression or stabilization occurs.4 While there is no effective cure, treatments include surgical resection, local irradiation, and systemic chemotherapy.4 Our patient's disease continued to progress despite local and systemic immunosuppression and resection. Although rare, Rosai-Dorfman disease can be confused with nodular scleritis and should be considered in patients with epibulbar masses and uveitis.
Correspondence: Dr Grossniklaus, Department of Ophthalmology, Emory Eye Center, 1365 B Clifton Rd, Room BT428, Atlanta, GA 30322 (firstname.lastname@example.org).
Author Contributions: All of the authors had full access to the data in this study. Dr Payne takes responsibility for the integrity of the data and the accuracy of the data analysis.
Financial Disclosure: None reported.
Funding/Support: This work was supported in part by a grant to Emory Eye Center from Research to Prevent Blindness, Inc, New York, New York.