Side Effects of Rituximab Injection for Fibrotic Hypersensitivity Pneumonitis
Rituximab treatment for fibrotic hypersensitivity pneumonitis can cause serious infusion-related reactions, infections, and pulmonary complications, with the most common side effects including infusion reactions, infections, and fatigue. 1
Common Side Effects
Infusion-related reactions are the most common adverse effects, typically occurring during the first infusion with onset between 30-120 minutes, and may include fever, chills, rigors, urticaria, pruritus, angioedema, nausea, fatigue, headache, throat irritation, rhinitis, vomiting, hypotension, flushing, and pain at disease sites 1
Gastrointestinal side effects including nausea, vomiting, diarrhea, and abdominal pain are frequently reported during rituximab treatment 2, 1
Infections are a significant concern due to B-cell depletion, with increased risk of bacterial, fungal, and viral infections that can be serious or even fatal 1
Constitutional symptoms such as fever, chills, body aches, and fatigue are commonly experienced during and after treatment 1, 2
Serious Adverse Effects
Pulmonary Complications
Rituximab-induced lung injury can manifest as interstitial lung disease, hypersensitivity pneumonitis, organizing pneumonia, or diffuse alveolar hemorrhage 3, 4
Symptoms of pulmonary toxicity include new or worsening dyspnea, cough, and hypoxemia, typically developing within days to weeks after rituximab administration 3, 4
Chest imaging may show new diffuse ground glass opacities in patients developing rituximab-induced lung injury 3
Treatment of rituximab-induced pulmonary toxicity typically requires discontinuation of the drug and administration of systemic corticosteroids 3, 4
Cytokine Release Syndrome
Cytokine release syndrome can occur when rituximab interacts with CD20 on lymphocytes, leading to fever, rigors, chills, and other constitutional symptoms 2, 5
This syndrome is more common in patients with high tumor burden and can range from mild symptoms to severe reactions requiring intensive care 5, 2
Tumor Lysis Syndrome
Tumor lysis syndrome can develop within 12-24 hours of the first infusion, causing kidney failure, abnormal heart rhythm, and electrolyte disturbances 1
Manifestations include increased serum creatinine, potassium, phosphate, lactate dehydrogenase, and uric acid levels 5
Severe Mucocutaneous Reactions
Severe skin reactions including Stevens-Johnson syndrome, lichenoid dermatitis, vesiculobullous dermatitis, and toxic epidermal necrolysis have been reported 1
These reactions can have variable onset, sometimes occurring on the first day of rituximab exposure 1
Serum Sickness-Like Reactions
- Serum sickness-like reactions with the classic triad of fever, rash, and arthralgia can develop, particularly in patients with underlying autoimmune conditions 6, 5
Hepatitis B Virus Reactivation
- HBV reactivation can occur in patients with current or prior HBV infection, potentially leading to fulminant hepatitis, hepatic failure, and death 1
Risk Stratification and Management of Infusion Reactions
Infusion reactions are classified by grade: grade 1 (cutaneous symptoms only), grade 2 (urticaria, nausea, vomiting, dyspnea), grade 3 (symptomatic bronchospasm, dyspnea, hypoxia), and grade 4 (anaphylaxis) 5
Management depends on reaction severity:
Preventive Measures
Premedication with acetaminophen and antihistamines before each infusion is recommended to reduce infusion-related reactions 1, 2
For patients with autoimmune conditions, methylprednisolone 100 mg IV or equivalent is recommended 30 minutes prior to each infusion 1
Screening for hepatitis B infection before initiating rituximab is essential to prevent viral reactivation 1
Close monitoring during infusion is crucial, particularly for patients with pre-existing cardiac or pulmonary conditions 1
Efficacy in Fibrotic Hypersensitivity Pneumonitis
In patients with chronic hypersensitivity pneumonitis, rituximab has shown potential to stabilize or improve lung function, with significant reduction in the rate of forced vital capacity (FVC) decline compared to pre-treatment periods 7
Rituximab could be considered as a salvage therapy in cases of severe hypersensitivity pneumonitis unresponsive to standard therapy, especially in patients with high risk of death 8
Important Considerations
The standard dosing for rituximab in autoimmune conditions is typically two 1000-mg doses given two weeks apart 5
Baseline immunoglobulin levels, hepatitis B and C antibody levels, and screening for latent tuberculosis should be performed prior to administering rituximab 5
Progressive multifocal leukoencephalopathy has been reported in patients treated with rituximab; caution should be used in immunosuppressed patients 5