# Late-Onset Neutropenia Induced by Rituximab in Rheumatic Diseases: A Report of Two Cases of Severe Presentation and a Literature Review

## TL;DR

This paper reports two severe cases of late-onset neutropenia caused by rituximab in patients with rheumatic diseases and emphasizes the importance of monitoring for this rare but serious side effect.

## Contribution

The paper contributes two new clinical case reports of severe late-onset neutropenia in rheumatic disease patients treated with rituximab.

## Key findings

- Two patients with rheumatic diseases developed severe febrile neutropenia after rituximab therapy.
- Both patients recovered after treatment with antibiotics and granulocyte colony-stimulating factor.
- Rituximab was discontinued in both cases due to the risk of recurring neutropenia.

## Abstract

Rituximab, a chimeric monoclonal antibody targeting the CD20 antigen on B cells, is widely used in oncological and immune-mediated diseases. However, late-onset neutropenia can occur, even in patients receiving concomitant immunosuppressants or chemotherapeutics, necessitating therapeutic adjustments. The development of neutropenia with rituximab monotherapy reinforces the relationship, but the exact pharmacological mechanism is still unknown. We report two cases of late-onset neutropenia after rituximab therapy: the first case is related to a woman with rheumatoid arthritis and anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis overlap and a history of alveolar hemorrhage; the second case concerns a woman with systemic lupus erythematosus and neurological manifestations. Both patients were hospitalized for febrile neutropenia, an unusual complication, and subsequently recovered after treatment with antibiotics and granulocyte colony-stimulating factor. Rituximab was discontinued. It is essential for rheumatologists to recognize and monitor for late-onset neutropenia during and after rituximab treatment, as early detection and intervention can prevent severe complications. The heterogeneity in clinical course observed in reported cases underscores the complexity of the condition and the impact on patient safety. The feasibility of resuming rituximab treatment after late-onset neutropenia requires careful evaluation.