Patient with GPA and Ocular Symptoms Successfully Treated with Rituximab in Case Report

A case report of a patient with granulomatosis with polyangiitis (GPA) along with ocular involvement suggests that Rituxan (rituximab) might be successful for people who don’t respond to prednisolone and cyclophosphamide.

The study, “Peripheral Ulcerative Keratitis Associated with Granulomatosis with Polyangiitis Emerging Despite Cyclophosphamide, Successfully Treated with Rituximab,” appeared in Internal Medicine, the journal of the Japanese Society of Internal Medicine.

GPA is a complex disease characterized by necrotizing granulomas — an area of inflammation where the tissue has died — and inflammation in small blood vessels, or vasculitis.

Approximately half of these patients have ocular, or eye, involvement. One of the complications related to ocular involvement in these patients is peripheral ulcerative keratitis (PUK), which can cause blindness.

The researchers presented a case of a GPA patient with ocular involvement, who did not respond favorably to the corticosteroid prednisolone and to intravenous infusion of the immunosuppressant cyclophosphamide (Cytoxan).

The patient had a history of hypertension, type 2 diabetes, and dyslipidemia, or abnormal amount of lipids in the blood.

The 67-year-old Japanese man was first admitted to the hospital complaining of ophthalmalgia (eye pain) and conjunctival hyperemia (a type of eye inflammation, characterized by redness) in his right eye.

The ocular symptoms first appeared 15 months before his hospital admission, which led to a diagnosis of scleritis — a painful inflammation of the white part of the eye — and ineffective treatment with eye drops containing corticosteroids and the immunosuppressant tacrolimus (sold as Prograf, among others).

Further exams revealed the patient was positive for proteinase-3 ANCA antibody. A new diagnosis of scleritis associated with ANCA-associated vasculitis (AAV) was them made, and the patient started a daily regimen of 30 mg prednisolone.

Although an initial improvement was noted, the scleritis ultimately worsened, leading to the addition of 150 mg cyclosporine daily, 11 months before the patient was admitted to the hospital.

The patient then began experiencing weight loss and sinusitis. As his scleritis worsened, he was hospitalized. An ophtalmologic exam revealed a nodule with bleeding in the upper ear-side of his right eye and aggravated inflammation. No notable findings were reported after chest, head, and kidney tests.

Due the right eye sinusitis and scleritis, as well as elevated levels of PR3-ANCA, the patient was then diagnosed with GPA. The physicians concluded that his chronic kidney disease was caused by diabetic nephropathy, or kidney inflammation.

The treatment regimen was then changed to an increased daily dose of oral prednisolone, following pulsed methylprednisolone and intravenous cyclophosphamide pulse therapy. In addition, the eye drops containing corticosteroids and tacrolimus were continued

The patient did not have eye pain for two weeks after starting treatment. However, his hyperemia remained. Also, the emergence of PUK and vitreous body in his right eye represented a significant risk for blindness.

The therapy was then changed to Rituxan (500 mg per body, 375 mg/m2 per week for four weeks). Peritectomy, a procedure to remove a strip of conjuntive tissue in eye surgery, was conducted to address the patient’s PUK, and membrane transplantation was done to resolve the thinning of his sclera (the white layer of the eyeball).

The new regimen led to a gradual improvement of inflammation, PUK, and hyperemia. The patient did not recover from the opacity in his vitreous body and from the significant loss of sight, but he was able to avoid blindness. Maintenance Rituxan was then administered at eight-month intervals. The patient’s symptoms did not relapse two years after the onset of Rituxan treatment.

The scientists hypothesize that one of the reasons why Rituxan was successful was the occurrence of vasculitis without granulomas.

“Following this hypothesis, as [Rituxan] may be an ideal first choice for ophthalmic GPA with vasculitic manifestations, it is necessary to clarify the relationships between the efficiency of [Rituxan] for GPA and the clinical and pathological aspects,” they wrote.

“The close cooperation of physicians and ophthalmologists may improve the ocular prognosis of GPA patients with ocular involvement,” the team concluded.

Rituxan, jointly marketed by Biogen and Genentech, is approved by the U.S. Food and Drug Administration for GPA.