RTX-Resistant Cryoglobulinemia with Glaucoma and Skin Ulcers

Yang CH, Qureshi AA, Churchill WH, Saavedra AP. Long-term Plasmapheresis in Conjunction With Thalidomide and Dexamethasone for the Treatment of Cutaneous Ulcers and Neovascular Glaucoma in Recalcitrant Type I CryoglobulinemiaJAMA Dermatol. (2014) 150(4):426-428. doi:10.1001/jamadermatol.2013.8700.

A patient with type I cryoglobulinemia, ulcers and glaucoma, refractory to rituximab, responded to plasmapheresis with thalidomide and dexamethasone with complete remission. This is important because rituximab failures with type I cryoglobulinemia are increasing.

A woman in her 50s with type I cryoglobuulinemia and bilateral lower extremity ulcers of one year’s duration developed new macules on her upper extremities and acute-angle closure glaucoma.

Laboratory tests were consistent with type I cryoglobulinemia secondary to plasma cell dyscrasia. A skin biopsy revealed capillary vascular proliferation with periodic acid-Shiff-positive material and no evidence of vasculitis.

The original leg lesions, at the pretibia and ankle, began to heal spontaneously after wound care, so she was followed with surveillance. Six months later, she developed erythematous, nonblanching macules on her upper extremities. This was followed by acute angle-closure glaucoma of the left eye, with venous engorgement and neovascularization of the iris. She was treated with emergency laser decompression followed by plasmapheresis.

The pain of the ulcers worsened, and new lesions developed. Because a bone marrow biopsy had revealed an interstitial infiltrate containing CD20⁺ B cells, she was given rituximab, which was discontinued after her ulcers continued to worsen.

She was treated with thalidomide (limited by thalidomide toxicity), dexamethasone, plasmapheresis, and standard wound care. After intensive plasmapheresis, the ulcers healed to complete closure and did not recur.

Iris neovascularization leading to glaucoma has been documented in cryoglobulinemia. Precipitation of cryoglobulins in the cooler peripheral regions of the eye may have led to anterior segment ischemia and aberrant angiogenesis in the iris.