439. Severe thrombocytopaenia after low-dose rituximab (RTX) for remission maintenance in limited granulomatosis with polyangiitis (GPA)

Presentation of Case: A 33 years-old female with limited (otorhinolaryngological manifestations) biopsy-proven granulomatosis with polyangiitis since age 15 is presented due to an uncommon serious adverse event. As main damage items, she has had a right mastoidectomy and subglottic stenosis. On remission for the last 10 years with methotrexate (MTX), with a maximum dose of 15 mg/week and during the last 5 years 10 mg/week and nasal mupirocin ointment due to S. aureus mucosal colonisation, she desired pregnancy in February 2020. Rituximab (RTX) was proposed as maintenance treatment after which she could proceed with her aim, and MTX was stopped. It was administered at 1 g with all previous necessary tests. The treatment proceeded uneventfully with usual premedication (hydrocortisone, diphenhydramine and chlorpheniramine). Two weeks later she presented vaginal, nasal, and gingival bleeding, and lower limb petechiae.

Diagnostic Testing: Blood cell count at the time of haemorrhagic manifestations: 2,000 platelets/uL, normal red blood cell, and leukocyte counts. Other routine laboratory tests were normal. CD19 and CD20 counts after RTX treatment remained depleted until September 2020 when they started to recover.

Differential & Final Diagnosis: RTX-induced severe thrombocytopaenia was the straightforward diagnosis. No other tests were performed due to the lack of other symptoms and the temporal relation with the first time prescribed RTX dose.

Discussion of Management: She was treated as an inpatient with 1 g IV methylprednisolone (3x on consecutive days) and platelet apheresis, and after four days discharged without complications. She continued with oral prednisone (PDN) with starting dose of 50 mg qd, which was gradually decreased until full stop on April 2020. She remained without treatment for GPA until February 2021 when she had photophobia, and after ophthalmological opinion, she was diagnosed with iridocyclitis. She was given PDN 10 mg qd and MTX was restarted up to 25 mg/week. She has remained in remission with no PDN and MTX 17.5 mg/week. The case presents these interesting points: a) the appearance of severe thrombocytopaenia due to RTX maintenance treatment for GPA, which has seldom been reported despite thrombocytopaenia being known as a potential adverse effect of RTX. Also, RTX is a therapeutic agent in immune-mediated thrombocytopaenia; b) the prolonged remission acquired with 1 g of RTX. She remained symptom-free until 5 months after CD19 and CD20 had recovered; c) the few options available for the safe treatment of GPA patients who desire, especially considering the GPA phenotype for which azathioprine or mycophenolate mofetil does not seem optimal long-term maintenance treatment options. Risk factors known for the development of RTX-induced thrombocytopaenia are basal counts less than 200,000/uL before RTX administration (the patient´s average platelet counts on the year prior to RTX administration was 350,000/uL), high platelet width distribution, haematologic malignancy as primary disease, and concomitant use of fluconazole or ciprofloxacin. None of them are present in this patient.

Conclusions: There is an unmet need for safe and effective treatments in patients who desire pregnancy.

Disclosures: Patient consent was obtained. There is nothing else to disclose.