Teaching lecture · Pediatric gastroenterology
Mechanisms, clinical phenotypes and treatment decisions
Anna
40 minutes teaching · 5 minutes discussion
Fictional case
adolescent with Crohn’s disease, infliximab restarted after a treatment interruption, then flushing, chest tightness and urticaria
Teaching vignette — not patient data
Teaching lecture · Pediatric gastroenterology
Mechanisms, clinical phenotypes and treatment decisions
Anna
40 minutes teaching · 5 minutes discussion
Fictional case
adolescent with Crohn’s disease, infliximab restarted after a treatment interruption, then flushing, chest tightness and urticaria
Teaching vignette — not patient data
Mechanisms
Adverse drug reaction — the broad category
Hypersensitivity — a clinical reaction resembling allergy
Drug allergy — an immune mechanism
Accurate documentation can preserve future therapeutic options.
Mechanisms
Minutes to hours
immediate patterns
Hours to days or weeks
delayed patterns
Drug administration
Record
Latency, dose number, objective signs and severity
Timing suggests possibilities but cannot diagnose the mechanism.
Mechanisms
Hapten or prohapten
drug-related antigen formation
Binds proteins or forms reactive metabolites
Pharmacological interaction with immune receptors
Interacts with HLA / T-cell receptor systems
Altered peptide presentation
Changes which peptides are presented
Conceptual models for small molecules — not proven for every drug or antibody.
Mechanisms
Step 1
Sensitization and drug-specific IgE
IgE bound to FcεRI
Step 2
Re-exposure activates mast cells and basophils
Cross-linking after relevant re-exposure
Step 3
Urticaria, angioedema, bronchospasm or hypotension
Mediators: skin, respiratory, circulatory
Anaphylaxis does not prove IgE; absent skin signs do not exclude anaphylaxis.
Mechanisms
Direct mast-cell activation
Complement-related pathways
Overlapping clinical presentations
Different pathways, similar presentations: treat anaphylaxis clinically.
Mechanisms
Type II
antibody-directed cell injury
Cell-bound target · e.g. cytopenia
Type III
immune-complex inflammation
Circulating complexes · may involve complement and organs
Fever, rash and arthralgia suggest an immune-complex pattern
Serum sickness-like illness can occur without demonstrated complexes.
Mechanisms
More common
Maculopapular drug eruptions
Severe cutaneous adverse reactions
DRESS, AGEP and SJS/TEN are distinct syndromes
Not a single uniform disease — DRESS may involve fever, facial edema and internal organs
Red flags
mucosal injury, skin pain, blistering or organ involvement
Red flags: urgent assessment, withdraw the culprit, no routine challenge for SCAR.
Mechanisms
The phenotype is suggestive rather than definitive.
Mechanisms
| Pattern | Typical timing | Clinical clues |
|---|---|---|
| Mast-cell pattern | Usually immediate | Urticaria, bronchospasm, circulatory compromise |
| Cytokine-release pattern | Often during or soon after administration | Fever, rigors, pain |
| Immune-complex pattern | Usually delayed | Fever, rash, arthralgia |
| T-cell pattern | Usually delayed | Eruption with syndrome-specific features |
Hypotheses, not boxes — severity drives treatment before the endotype is known.
IBD biologics
α
cytokine-related effects
β
hypersensitivity against the biologic
γ
immune imbalance
δ
cross-reactivity
ε
nonimmune effects
Not every adverse event caused by a biologic is hypersensitivity.
IBD biologics
Potential immune target: anti-drug antibodies
Humanization reduces some determinants but does not guarantee tolerance.
IBD biologics
| Target | Examples | Route |
|---|---|---|
| TNF | Infliximab, adalimumab | IV and/or SC depending on agent and formulation |
| α4β7 integrin | Vedolizumab | IV; SC maintenance in selected settings |
| IL-12/23 p40 | Ustekinumab | IV induction, SC maintenance for IBD |
| IL-23 p19 | Risankizumab, mirikizumab, guselkumab | Agent-specific IV/SC regimens |
JAK inhibitors and S1P modulators are small molecules, not biologic antibodies.
A target map, not an approval list — verify local pediatric labeling.
IBD biologics
Infusion event
Restarted after interruption · urticaria · chest tightness
Immediate hypersensitivity
Cytokine-release or mixed phenotype
Possible immune-complex and complement involvement
Mechanism may remain uncertain after workup.
IBD biologics
Anti-drug antibodies
Altered clearance and reduced exposure
Association with reaction risk
Routine antibody assays do not establish drug-specific IgE
A negative assay does not guarantee safe re-exposure.
IBD biologics
Pattern 1
Fever, rash and arthralgia after treatment
Serum sickness or serum-sickness-like illness; evaluate competing diagnoses
Pattern 2
Delayed drug eruption
Assess morphology and systemic involvement
Pattern 3
New psoriasiform lesions during anti-TNF therapy
May be paradoxical psoriasis
Paradoxical psoriasis is immune dysregulation, not IgE allergy.
IBD biologics
Vedolizumab
infusion and hypersensitivity reactions
Ustekinumab
serious hypersensitivity can occur
IL-23 inhibition
serious hypersensitivity remains possible
Serious reactions including anaphylaxis are documented in current product information. Do not compare rates across unlike trials.
Rare reactions remain possible with newer therapies.
IBD biologics
Local
pain, erythema, swelling or persistent plaque
Irritation or immune · assess technique, formulation, recurrence
Systemic
generalized urticaria, respiratory or circulatory symptoms
Requires a different response and future assessment
Timing, distribution and evolution guide assessment
A local reaction alone does not establish systemic allergy.
Management
1
Stop administration and call for help
2
Assess airway, breathing and circulation
3
Give IM epinephrine promptly for suspected anaphylaxis
4
Provide supportive care and reassess
Follow the institutional pediatric emergency protocol. Do not delay treatment for tryptase or a mechanistic diagnosis.
Antihistamines and corticosteroids do not replace IM epinephrine.
Management
Reaction onset
Acute tryptase
Ideally within 2 hours, without delaying treatment
Symptom resolution
Baseline tryptase
Generally ≥24 h after resolution
Document
Exact timing, objective findings and treatment response; dose, infusion rate, prior exposures, concomitant medicines
Supports mast-cell activation
Acute > 1.2 × baseline + 2 ng/mL
A rise does not prove IgE mediation
A normal tryptase does not exclude anaphylaxis; a rise does not prove IgE.
Management
| Clinical question | Assessment |
|---|---|
| What was the clinical syndrome? | Detailed history and records |
| Is a specific allergic mechanism supported? | Selected specialist testing |
| Has immunogenicity affected exposure? | Drug concentration and anti-drug antibodies |
A negative result is not clearance for unmonitored exposure.
Management
After recovery
Individualized risk assessment
Selected mild nonallergic event
adjusted infusion strategy
Uncertain low-risk history
specialist-supervised challenge
Essential drug with suitable hypersensitivity phenotype
desensitization
Alternative treatment when indicated
Desensitization induces temporary tolerance; it does not exclude allergy.
Management
It does not permanently remove the allergy.
Management
Practice
Consistent treatment delivery and individualized immunogenicity management
Evidence
Universal premedication has limited supporting evidence
Evidence
Rapid infusion evidence depends on patient selection
Practice
A written plan for the next administration
Document the plan jointly: gastroenterology, allergy, nursing and the family.
Back to the case · Management
1
Treat the acute syndrome according to severity
2
Use the clinical history and targeted workup
3
Choose and document the future treatment pathway
Discussion · 5 minutes