What is the role of Rituximab (rituximab) infusion in the treatment of Henoch-Schonlein Purpura (HSP)?

Rituximab for Henoch-Schönlein Purpura

Rituximab should be reserved for chronic, steroid-dependent or refractory Henoch-Schönlein purpura (HSP) that has failed conventional corticosteroid therapy and other immunomodulatory agents, particularly in cases with severe renal involvement, persistent skin manifestations, or recurrent hospitalizations. This recommendation is based on case series demonstrating clinical remission and steroid-sparing effects in patients who had exhausted standard treatment options.

Clinical Context and Evidence Base

The evidence for rituximab in HSP comes exclusively from case reports and small case series, not from randomized controlled trials or formal guidelines. The largest published experience includes 8 pediatric patients with chronic steroid-dependent HSP who achieved clinical remission following rituximab therapy 1. In this cohort, 7 out of 8 children met remission criteria (defined as absence of active rash, arthritis, nephritis, or gastrointestinal symptoms), with significant reduction in oral corticosteroid burden from 0.345 mg/kg/day pre-treatment to 0 mg/kg/day at 2 years post-treatment (p = 0.03) 1.

Specific Indications for Rituximab Use

Consider rituximab when the following criteria are met:

• Chronic steroid-dependent disease: Patients requiring continuous corticosteroids for >6-8 weeks with disease flares upon tapering 1
• Failure of conventional immunomodulatory agents: Inadequate response to azathioprine, mycophenolate, or cyclophosphamide 1, 2
• Severe renal involvement: Progressive nephritis with crescentic glomerulonephritis, significant proteinuria (>1 g/day), or declining renal function 3
• Recurrent hospitalizations: Multiple admissions for HSP complications despite standard therapy 1
• Severe extra-renal manifestations: Persistent skin vasculitis, neurologic involvement (such as sciatic peroneal nerve involvement), or refractory abdominal pain 2, 4

Dosing Regimen

The most commonly reported rituximab dosing protocols in HSP include:

• Standard lymphoma protocol: 375 mg/m² weekly for 4 consecutive weeks 1
• Rheumatoid arthritis protocol: Two infusions of 1,000 mg given two weeks apart 2, 3

Both regimens have demonstrated efficacy, though the optimal dosing strategy remains undefined due to limited data 1, 2.

Expected Outcomes and Timeline

Clinical improvement typically occurs within weeks to months:

• Reduction in hospitalizations: Median hospitalizations decreased from 1.5 pre-treatment to 0-1 post-treatment 1
• Steroid discontinuation: Most patients achieved complete corticosteroid cessation within 6-24 months 1, 2
• Sustained remission: Follow-up data extending to 2 years demonstrate durable responses without serious adverse events 1, 2

Safety Considerations and Monitoring

Rituximab carries specific risks that require vigilant monitoring:

• Infusion reactions: Occur in approximately 20% of patients, typically manageable with premedication 5, 6
• Infectious complications: Screen for hepatitis B before initiation; monitor for reactivation and opportunistic infections 6
• Hypogammaglobulinemia: Risk increases with multiple courses; monitor serum immunoglobulin levels regularly 6
• Rare severe complications: Progressive multifocal leukoencephalopathy and severe mucocutaneous reactions have been reported, though exceedingly rare 6

Required baseline and monitoring tests include:

• Complete blood count with differential 5
• Hepatitis B surface antigen, core antibody, and surface antibody 6
• Serum immunoglobulin levels (IgG, IgA, IgM) 5
• Renal function (creatinine, urinalysis with microscopy) 3
• Hepatic function panel 5

Critical Caveats

Important limitations of the evidence:

• All published data consists of case reports and small case series without control groups 1, 2, 3, 7, 4
• No standardized criteria exist for defining "refractory" HSP that warrants rituximab therapy 1
• Long-term safety data beyond 2 years in HSP patients is lacking 1
• The mechanism of rituximab's efficacy in HSP (an IgA-mediated vasculitis) remains unclear, as rituximab depletes CD20+ B cells but does not directly target IgA-producing plasma cells 1

Do not use rituximab as first-line therapy for HSP. Standard treatment with corticosteroids (typically prednisone 1-2 mg/kg/day for 2-4 weeks with gradual taper) should be attempted first, with conventional steroid-sparing agents (azathioprine, mycophenolate) tried before escalating to rituximab 1, 2.

Practical Implementation

When initiating rituximab for refractory HSP:

• Ensure adequate trial of corticosteroids (minimum 6-8 weeks) and at least one conventional immunomodulatory agent 1
• Document objective disease activity (proteinuria quantification, photographic documentation of rash, frequency of hospitalizations) to assess treatment response 1, 3
• Administer appropriate premedication (acetaminophen, antihistamines, and sometimes corticosteroids) to minimize infusion reactions 5
• Plan for B-cell monitoring (CD19 or CD20 counts) to document adequate B-cell depletion, though correlation with clinical response is imperfect 1
• Continue monitoring for disease activity for at least 2 years post-treatment, as late relapses can occur 1, 2