Dr Jasmine H. Francis and colleagues have reported a case of Refractory Nodular Scleritis that has been published in the journal of American Medical Association.
Scleritis is a chronic, painful, and potentially blinding inflammatory disease.It is characterized by edema and cellular infiltration of the scleral and episcleral tissues. It has an underlying cause, usually an autoimmune disease including rheumatoid arthritis, granulomatosis with polyangiitis, other vasculitic/connective tissue diseases.
According to history, 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. 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.
The patient was diagnosed having Episcleral-uveal nodule and uveitis associated with histiocytosis. Next line was 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 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. 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.
Histiocytoses are rare hematologic disorders characterized by pathological accumulation and infiltration of activated histiocytes in affected tissues, including ophthalmic structures. The non– Langerhans cell histiocytoses include RDD disease and are clinically heterogenous, including vision-threatening structures (such as the orbit, uveal tract, optic nerves, or the hypothalamic-pituitary adrenal axis). This case demonstrated an episcleral nodule with sclerouveal infiltration seen with ultrasound biomicroscopy. Despite oral and topical steroids, she had no improvement.
Because histiocytic neoplasms are hematologic in their pathogenesis, authors considered intra-arterial melphalan as a potential therapeutic option. Melphalan is an alkylating agent of mustard gas derivation used for blood-based neoplasms, notably multiple myeloma. The advantage of intra-arterial chemotherapy is delivering a therapeutic dose to the target lesion while minimizing systemic administration.
This patient had no myelosuppression or other systemic toxic reactions following her 3 courses of 9-mg intra-arterial melphalan. Instead, she had a sustained ocular response, which allowed her to discontinue systemic steroids, oral nonsteroidal anti-inflammatory drugs, and all eye drops. She continued to have a sustained response at 10 months' follow-up.
In summary, authors highlighted that ocular histiocytosis may masquerade as refractory nodular scleritis. They describe implementation of intra-arterial chemotherapy for this vision-threatening intraocular histiocytosis with sclerouveal infiltration. This treatment approach might benefit from broader evaluation of its feasibility and safety across a variety of tumor sites and arterial targets, as well as its efficacy.
Source: Jasmine H. Francis, MD; Y. Pierre Gobin, MD; Eli L. Diamond, MD; JAMA Ophthalmology Clinical Challenge
doi: 10.1001/jamaophthalmol.2022.3591