What is the role of plasmapheresis in treating autoimmune diseases?

Role of Plasmapheresis in Treating Autoimmune Diseases

Plasmapheresis is recommended as a therapeutic option for specific autoimmune diseases, primarily as a second or third-line treatment for patients with severe symptoms who have failed conventional therapies. 1

Mechanism of Action

• Plasmapheresis is an extracorporeal therapy that separates and removes plasma containing pathogenic elements (such as autoantibodies, immune complexes, and cytokines) from the patient's blood while returning the cellular components 1
• The removed plasma is typically replaced with albumin, fresh-frozen plasma, or crystalloid solutions before being returned to the patient 1
• The procedure effectively reduces circulating autoantibodies and immune complexes, providing rapid but temporary relief in autoimmune conditions 1

Primary Indications in Autoimmune Diseases

Neurological Disorders

• First-line therapy for severe Guillain-Barré syndrome with high-quality evidence supporting its use 1
• Recommended for myasthenia gravis with significant symptoms, with moderate evidence strength 1
• Treatment option for severe immune-mediated neuropathies, especially those with rapid progression 1

Renal Conditions

• Recommended for ANCA-associated vasculitis requiring dialysis or with rapidly increasing serum creatinine 1
• Used in anti-glomerular basement membrane (anti-GBM) disease with moderate evidence strength 1
• Beneficial in severe cryoglobulinemia with acute kidney involvement 1

Pulmonary Autoimmune Conditions

• Suggested for patients with confirmed autoimmune pulmonary alveolar proteinosis (aPAP) who remain significantly symptomatic despite receiving exogenous GM-CSF and rituximab 2
• Recommended for patients with diffuse pulmonary hemorrhage in ANCA vasculitis 1

Dermatological Autoimmune Conditions

• Recommended in refractory cases of pemphigus vulgaris when combined with corticosteroids and immunosuppressants 1
• Not recommended as routine treatment for newly diagnosed pemphigus but may be considered in refractory cases 1

Treatment Protocol Considerations

• Plasmapheresis should generally be combined with immunosuppressive medications to prevent rebound antibody production 1
• Timing is critical when used with other therapies - rituximab should be administered after plasmapheresis since the procedure removes the drug 1
• For autoimmune pulmonary alveolar proteinosis, higher intensity plasmapheresis regimens may be needed to successfully suppress GM-CSF autoantibodies 2
• The optimal number of sessions varies by condition, but evidence suggests 4 sessions may be optimal for conditions like myasthenia gravis 3

Safety and Adverse Effects

• Mortality associated with plasmapheresis is low, estimated at 0.05% based on systematic reviews 2, 4
• Common complications include blood pressure instability due to rapid fluid shifts during the procedure 4
• Removal of clotting factors can lead to coagulation defects 4
• Increased infection risk due to removal of immunoglobulins 4
• When combined with immunosuppressants, there is increased risk of opportunistic infections requiring prophylactic measures 1

Evidence Quality and Limitations

• For many autoimmune conditions, evidence supporting plasmapheresis comes from case reports rather than randomized controlled trials 2
• In autoimmune pulmonary alveolar proteinosis, evidence is of very low quality and arises from case reports only 2
• Spontaneous remission is observed in some autoimmune conditions, making it difficult to establish treatment effect based on available case reports 2
• Benefits are often subjective and not based on validated measurement instruments 2

Clinical Decision Algorithm

1. First-line consideration: Reserve for specific conditions with strong evidence (Guillain-Barré syndrome, myasthenia gravis crisis, anti-GBM disease) 1
2. Second/third-line consideration: For patients with severe autoimmune disease refractory to conventional treatments 1
3. Patient selection factors:
   • Severity of disease (significant symptoms despite conventional therapy) 2
   • Presence of measurable autoantibodies that can be removed 1
   • Failure of conventional immunosuppressive therapy 2
4. Treatment protocol determination:
   • Disease-specific protocols (number of sessions, frequency, replacement fluid) 1
   • Combination with appropriate immunosuppressive therapy 1
   • Monitoring of clinical response and antibody levels when possible 1