Figure 1. Photographs of the left sclera prior to surgical excision of the mass (A) and 1 year after surgical excision and 8 months after initiation of cyclosporine therapy (B), and photographs of the right sclera prior to cyclosporine treatment (C) and 8 months after initiation of cyclosporine therapy (D).
Figure 2. Photomicrographs of the left scleral mass biopsy specimen. A, Histiocytes, lymphoid cells, and plasma cells are present. Arrow indicates lymphophagocytosis by histiocytes (emperipolesis), characteristic of Rosai-Dorfman disease (hematoxylin-eosin, original magnification ×600). B, The S-100 protein immunostain characteristically stains histiocytes of Rosai-Dorfman disease (original magnification ×400). C, The stain for CD68 is expressed by histiocytes (original magnification ×400).
Shah A, Bielory L, Mirani N, Tu Y, Chu DS. Epibulbar Rosai-Dorfman Disease: Novel Manifestation and Treatment. Arch Ophthalmol. 2012;130(9):1218-1220. doi:10.1001/archophthalmol.2012.12
Author Affiliations: Institute of Ophthalmology and Visual Science (Ms Shah and Drs Tu and Chu) and Department of Pathology (Dr Mirani), New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, Department of Environmental Sciences, Rutgers University, New Brunswick (Dr Bielory), STARx Allergy and Asthma Center, Springfield (Dr Bielory), and Metropolitan Eye Research and Surgery Institute, Palisades Park (Dr Chu).
Sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease [RDD]) is a benign, idiopathic, self-limiting lymphoproliferative disease, described by Rosai and Dorfman in 1969.1 Extranodal manifestations represent about 43% of cases.2 The disease is classically accompanied by fever, malaise, leukocytosis, increased erythrocyte sedimentation rate, and hypergammaglobulinemia.1
Rosai-Dorfman disease is diagnosed histopathologically, with abundant histiocytes often engulfing lymphocytes and lymphoid cells, known as emperipolesis. The histiocytes are characteristically reactive to CD68 and S-100 proteins.1
Herein, we discuss the unique case and treatment of a woman who had RDD with bilateral epibulbar lesions concurrent with anterior uveitis.
A 36-year-old woman with painful ocular erythema, photophobia, and decreased vision bilaterally for 8 months was referred to the Institute of Ophthalmology and Visual Science at New Jersey Medical School for sclerouveitis. She had no previous ocular history, but she had a medical history of hypertension and diabetes mellitus. On examination, her corrected visual acuities were 20/25 OD and 20/60 OS. Slitlamp examination showed trace cell and flare in the left anterior chamber and nontender, fixed erythematous nodules in the perilimbal sclera bilaterally. Systemic evaluation findings were normal, and laboratory results showed a Westergren erythrocyte sedimentation rate of 49 mm/h. Her sclerouveitis had partially responded to prior treatment with topical and oral corticosteroids; however, this treatment was discontinued at her initial visit owing to her cushingoid appearance.
The well-circumscribed mass in the left eye (Figure 1A) was completely surgically excised. Histopathologically, it demonstrated large, periodic acid–Schiff–positive, CD68 protein–and S-100 protein–immunoreactive histiocytic cells with emperipolesis, characteristic of RDD (Figure 2).
Laboratory results 3 months after excision showed an elevated γ-globulin level (1.8 g/dL) and an increased erythrocyte sedimentation rate (36 mm/h). Chest and paranasal sinus radiographic findings were normal with no lymphadenopathy.
Four months after excision, the patient developed a rapidly growing, thick, 8 × 8-mm, vascularized mass on the right eye (Figure 1C). She refused a second surgery; oral cyclosporine was initiated. After 8 months of treatment (100 mg/d), the lesion regressed to 6 × 6 mm, appearing flatter and less erythematous (Figure 1D). She reported resolution of associated tenderness and redness. The left eye remains quiescent (Figure 1B), and neither eye shows uveitis.
The most common manifestation of RDD is painless cervical lymphadenopathy.1,2 Fewer than 10% of cases include ocular involvement, primarily in the orbit or adnexa.2 Around 20 cases with epibulbar involvement have been reported. Of the few with concurrent uveitis and scleritis, only ours involves bilateral epibulbar masses associated with uveitis as the sole manifestation.
Also, to our knowledge, this is the first reported case of RDD treated with systemic cyclosporine. Although cyclosporine inhibits T-lymphocyte interleukin 2 (IL-2) release, biopsy findings of the left epibulbar mass were negative for upregulated IL-2 receptors (CD25), contrasting with CD25 positivity reported in the literature.3 We postulate that the negative findings were a result of chronic steroid treatment. The histiocytes involved in RDD are immunophenotypically similar to recently differentiated, activated macrophages.3 Thus, we propose that the effectiveness of cyclosporine treatment may be due to cyclosporine's inhibition of cyclophilin A, a potent monocytic chemoattractant.4
Most patients with RDD improve spontaneously.5 Treatments most commonly reported include surgery, corticosteroids, chemotherapy (alkylating agents, antimetabolites, vinca alkyloids), radiation, or a combination thereof.5 Surgical excision is often the first-line therapy in patients with ocular manifestation; however, outcomes of both surgical and medical therapy are inconsistent, frequently yielding no more than a partial response.6
In our case, surgical excision and cyclosporine treatment in the left eye showed complete symptom resolution after 1 year. Cyclosporine treatment led to shrinkage of the rapidly growing lesion in the right eye with decreased vascularity. The patient reported that she was comfortable and steroid independent. Although producing a limited response when used alone, cyclosporine may be a useful therapeutic tool as an adjunct to surgery or when surgery is refused.
Correspondence: Dr Chu, Institute of Ophthalmology and Visual Science, Doctor's Office Center, 90 Bergen St, Ste 6100, Newark, NJ 07103-2499 (firstname.lastname@example.org).
Financial Disclosure: None reported.