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Treatment-Refractory Nodular Scleritis

Educational Objective
Based on this clinical scenario and the accompanying image, understand how to arrive at a correct diagnosis.
1 Credit CME

A 59-year-old woman with a 5-year history of intermittent bilateral uveitis and scleritis presented with painful left uveitis and an episcleral nodule (Figure 1). Ultrasound biomicroscopy revealed an elevated and tender uveal-episcleral lesion. Visual acuity was 20/30 in the left eye and 20/25 in the right eye. She had been taking 60 mg of oral prednisone; topical prednisolone acetate, 1%; and oral ibuprofen for 10 days without relief. She was suspected of being a steroid responder due to elevated intraocular pressure bilaterally. Three years prior, sinus pressure symptoms led to magnetic resonance imaging that revealed a nasal sinus mass. Biopsy demonstrated a histiocytic infiltrate with emperipolesis, consistent with Rosai-Dorfman-Destombes (RDD) disease. Timolol-dorzolamide topical drops were initiated. Staging evaluations showed no other sites of RDD disease.

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Episcleral-uveal nodule and uveitis associated with histiocytosis

C. Consider treating the left eye with intra-arterial melphalan

Uveitis and episcleral/uveal tract nodules can be manifestations of RDD disease, but RDD disease can be refractory to steroids, making an alternative treatment necessary. RDD disease is a subtype of histiocytosis, in which clonal expansion of activated histiocytes accumulate in tissues including the lymph nodes and possibly the eye. Given the myelogenous derivation of histiocytic disease, targeted delivery of melphalan (choice C) is emerging as a treatment option for isolated, symptomatic disease, particularly of ocular structures. It is standard care for retinoblastoma and has few adverse events.1 Following 3 monthly infusions of intra-arterial melphalan (9 mg) administered to the ophthalmic artery, the episcleral/uveal nodule regressed, the pain abated, oral steroids and all topical drops were discontinued, and the corrected visual acuity improved to 20/20 (Figure 2).

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Article Information

Corresponding Author: Jasmine H. Francis, MD, Ophthalmic Oncology Service, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY 10065 (francij1@mskcc.org).

Published Online: September 15, 2022. doi:10.1001/jamaophthalmol.2022.3591

Conflict of Interest Disclosures: Dr Gobin has stock ownership in and is chief executive officer of Serenity Medical Inc. Dr Diamond received consulting fees from Springworks Therapeutics and Day One Biopharmaceuticals and unpaid editorial support from Pfizer. No other disclosures were reported.

Funding/Support: This study was supported by philanthropic funding from The Fund for Ophthalmic Knowledge (Dr Francis), Cancer Center Support grant P30 CA008748 (Drs Francis and Diamond), the Frame Family Fund (Dr Diamond), the Applebaum Foundation, and the Joy Family West Foundation (Dr Diamond).

Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Additional Contributions: We thank David H. Abramson, MD, for his contributions to this work. We thank the patient for granting permission to publish this information.

Francis  JH , Abramson  DH , Gobin  YP ,  et al.  Electroretinogram monitoring of dose-dependent toxicity after ophthalmic artery chemosurgery in retinoblastoma eyes: six year review.   PLoS One. 2014;9(1):e84247. doi:10.1371/journal.pone.0084247PubMedGoogle ScholarCrossref
Abla  O , Jacobsen  E , Picarsic  J ,  et al.  Consensus recommendations for the diagnosis and clinical management of Rosai-Dorfman-Destombes disease.   Blood. 2018;131(26):2877-2890. doi:10.1182/blood-2018-03-839753PubMedGoogle ScholarCrossref
Diamond  EL , Dagna  L , Hyman  DM ,  et al.  Consensus guidelines for the diagnosis and clinical management of Erdheim-Chester disease.   Blood. 2014;124(4):483-492. doi:10.1182/blood-2014-03-561381PubMedGoogle ScholarCrossref
Nasany  RA , Reiner  AS , Francis  JH , Abla  O , Panageas  KS , Diamond  EL .  Rosai-Dorfman-Destombes disease of the nervous system: a systematic literature review.   Orphanet J Rare Dis. 2022;17(1):92. doi:10.1186/s13023-022-02220-0PubMedGoogle ScholarCrossref
Falco  P , Bringhen  S , Avonto  I ,  et al.  Melphalan and its role in the management of patients with multiple myeloma.   Expert Rev Anticancer Ther. 2007;7(7):945-957. doi:10.1586/14737140.7.7.945PubMedGoogle ScholarCrossref
Steiner  M , Matthes-Martin  S , Attarbaschi  A ,  et al.  Improved outcome of treatment-resistant high-risk Langerhans cell histiocytosis after allogeneic stem cell transplantation with reduced-intensity conditioning.   Bone Marrow Transplant. 2005;36(3):215-225. doi:10.1038/sj.bmt.1705015PubMedGoogle ScholarCrossref
Francis  JH , Gobin  YP , Alshiekh Nasany  R ,  et al.  Intra-arterial melphalan for neurologic non-Langerhans cell histiocytosis.   Neurology. 2021;96(23):1091-1093. doi:10.1212/WNL.0000000000012070PubMedGoogle ScholarCrossref
Gobin  YP , Cloughesy  TF , Chow  KL ,  et al.  Intraarterial chemotherapy for brain tumors by using a spatial dose fractionation algorithm and pulsatile delivery.   Radiology. 2001;218(3):724-732. doi:10.1148/radiology.218.3.r01mr41724PubMedGoogle ScholarCrossref
AMA CME Accreditation Information

Credit Designation Statement: The American Medical Association designates this Journal-based CME activity activity for a maximum of 1.00  AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to:

  • 1.00 Medical Knowledge MOC points in the American Board of Internal Medicine's (ABIM) Maintenance of Certification (MOC) program;;
  • 1.00 Self-Assessment points in the American Board of Otolaryngology – Head and Neck Surgery’s (ABOHNS) Continuing Certification program;
  • 1.00 MOC points in the American Board of Pediatrics’ (ABP) Maintenance of Certification (MOC) program;
  • 1.00 Lifelong Learning points in the American Board of Pathology’s (ABPath) Continuing Certification program; and
  • 1.00 CME points in the American Board of Surgery’s (ABS) Continuing Certification program

It is the CME activity provider's responsibility to submit participant completion information to ACCME for the purpose of granting MOC credit.

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