What is the process for food desensitization, specifically oral immunotherapy (OIT) and sublingual immunotherapy (SLIT)?

Food Desensitization Process

Food desensitization through oral immunotherapy (OIT) and sublingual immunotherapy (SLIT) are currently investigational approaches that should only be performed in specialized research centers or clinical centers with extensive experience, as neither therapy is FDA-approved for routine clinical use in the United States. 1

Current Guideline Position

The NIAID-sponsored expert panel does not recommend using allergen-specific immunotherapy to treat IgE-mediated food allergy outside of highly controlled research settings due to insufficient safety and efficacy data, despite promising preliminary results. 1 This conservative stance reflects the risk of severe reactions including anaphylaxis during both in-office and home dosing phases. 1

Oral Immunotherapy (OIT) Process

Mechanism and Protocol Structure

OIT involves repeated oral exposure to incremental amounts of food allergen, starting with very dilute concentrations and gradually increasing until a maintenance dose is reached. 1 The process theoretically induces immune system changes by:

• Promoting regulatory T cells modulated by transcription factor FoxP3 1
• Upregulating allergen-specific IgG4 while decreasing IgE 1, 2
• Mediating changes through interleukin 10 and transforming growth factor β 1

Dosing Approaches

Low-dose protocols (300 mg/day) achieve similar sustained desensitization to high-dose protocols (3000 mg/day) with potentially improved safety profiles. 1 The allergen is immediately swallowed during OIT, distinguishing it from sublingual approaches. 3

Treatment Phases

OIT requires continuous reexposure to maintain desensitization, which is distinct from true tolerance that allows interrupted exposure. 1 Most patients can be successfully desensitized with limited adverse events in controlled settings. 1

Sublingual Immunotherapy (SLIT) Process

Administration Method

SLIT involves placing allergen drops or tablets under the tongue, which are either held sublingually and spit out or swallowed. 1 The allergen is taken up by mucosal antigen-presenting cells (Langerhans cells, myeloid dendritic cells) through a mechanism distinct from OIT. 1, 4

Safety Profile

SLIT demonstrates a very low incidence of anaphylactic or life-threatening reactions compared to OIT. 1 Adverse effects are generally limited to:

• Mild oropharyngeal symptoms (oral pruritus) 1
• Pruritic cutaneous reactions 1
• Gastrointestinal symptoms (diarrhea, abdominal pain) 1

Critical Limitations and Safety Concerns

Desensitization vs. Tolerance

Desensitization requires continuous allergen exposure and does not equal true tolerance. 1 After 24 months of egg OIT, only 28% of patients achieved sustained unresponsiveness after discontinuing treatment for 8 weeks. 1 Tolerance lasting 2-6 weeks after treatment interruption has been demonstrated in limited studies. 1

Adverse Events

Patients in OIT trials have suffered anaphylaxis during both in-office and home dosing phases, with some participants withdrawing due to severe reactions or inability to progress through protocols. 1 Systemic reactions can occur at previously tolerated doses, especially after exercise or viral illness. 1

Unknown Long-Term Outcomes

Long-term outcomes for both therapies remain unknown, including:

• Development of sustained tolerance 1
• Risk of eosinophilic esophagitis (EoE) 1
• Efficacy in young patients or those with severe reactivity 1

Emerging Approaches

Multi-Food OIT with Biologics

Multi-food OIT with adjunctive omalizumab (anti-IgE antibody) has been shown to rapidly decrease time to desensitization for multiple foods simultaneously. 1 This approach addresses the burden for patients with multiple food allergies (approximately 45% of individuals with food allergy). 1 Research into combination therapy with dupilumab is ongoing. 1

Alternative Routes

Epicutaneous immunotherapy (EPIT) and vaccine approaches are under investigation as additional therapeutic options. 1, 3

Clinical Implementation Requirements

Setting Requirements

These therapies are currently in highly experimental phase 1/2a trials and should only be administered in:

• Research centers participating in NIH-sponsored studies 1
• Clinical centers with extensive FA-AIT experience 3
• Settings with immediate access to anaphylaxis management 1

Patient Selection Considerations

Real-life OIT studies are enrolling patients based on history and positive serum-specific IgE or skin prick test results without oral food challenges to reduce screening barriers. 1 However, this approach requires careful risk-benefit assessment given the potential for severe reactions. 1

Common Pitfalls

Do not confuse desensitization (temporary protection requiring continuous exposure) with tolerance (sustained protection after treatment discontinuation). 1 The exact mechanism of action remains unclear, and efficacy varies significantly between individuals. 1

Avoid off-label prescribing of these therapies outside controlled research settings despite evidence of such practices among some allergists and otolaryngologists. 1 The risk-benefit profile has not been established for routine clinical use. 1

Ensure patients understand that multiple clinic visits over months to years are required, and fear of adverse reactions during screening oral food challenges remains a significant barrier. 1