Allergy

Question 1

Food protein-induced enterocolitis (FPIES)
Outline the pathogenesis, presentation & complications of FPIES.
What is the common age range, treatments

Answer 1

Food protein-induced enterocolitis is not Ig-E mediated, but an example of cell mediated hypersensitivity. It presents with irritability and protracted vomiting 1-3 hours after feeding, and chronically can cause bloody diarrhoea and bloating. Hypotension occurs in about 15%.

Question 2

IgE Mediated Food Allergy

Answer 2

IgE-mediated immediate-onset food sensitivity. Type I reactions (i.e. immediate hypersensitivity reactions) involve IgE–mediated release of histamine and other mediators from mast cells and basophils, which are the key mediators in anaphylaxis. Continuous or repeated exposure to an can result in chronic allergic inflammation. Tissue from sites of chronic allergic inflammation contains eosinophils and T cells (particularly TH2 cells). Eosinophils can release many mediators (e.g. major basic protein), which can cause tissue damage and thus increase inflammation. This can result in structural and functional changes to the affected tissue.

Furthermore, a repeated allergen challenge can result in increased levels of antigen-specific IgE, which ultimately can cause further release of IL-4 and IL-13, thus increasing the propensity for TH2 cell/IgE–mediated responses.

Question 3

Type 1 Hypersensitivity Reactions
Outline the process.
What are some examples

Question 4

Type 2 Hypersensitivity Reactions
Outline the process.
What are some examples

Question 5

Type 3 Hypersensitivity Reactions
Outline the process.
What are some examples

Question 6

Type 4 Hypersensitivity Reactions
Outline the process.
What are some examples

Question 7

Red Man Syndrome
Outline pathophysiology, what medications typically cause?
What are other symptoms

Answer 7

“Red Man Syndrome” or “Red Neck Syndrome” is a response by mast cell degranulation releasing histamine and characterized by a red flushing of the upper body/face and is more common in children than adults. It may be accompanied commonly by headache, agitation, fever chills and tingling of the mouth rarely, hypotension and angioedema can manifest. It usually occurs on the first infusion of IV vancomycin: it is not considered to be an allergic/type I hypersensitivity reaction. To avoid causing this reaction, it is recommended that IV vancomycin be administered at a slower rate, or antihistamines

Question 8

Large Local Reaction (LLR)
Define, outline pathophysiology and treatments. What is the risk of systemic reaction after LLR?

Answer 8

Large local reactions develop over hours to days, and involve swelling of extensive areas >10 cm that are contiguous with the sting site, and may last for days. Localised skin responses to biting insects are likely caused by vasoactive or irritant materials derived from insect saliva (not IgE), thus antihistamines may not have a significant response except for symptom control of itch. For local cutaneous reactions, treatment with cold compresses, topical medications to relieve itch and occasionally the use of a systemic antihistamine or oral analgesic are appropriate. Steroids may have some effect in reducing inflammation but are not required. Remove any sting present by scraping. The risk of a systemic reaction after a large local reaction is only 5-10%, thus, venom immunotherapy is not recommended and carrying an Epipen is considered optional.

Question 9

Bee Venom Anaphylaxis
What species of bees are included in hymenoptera? What is the risk of recurrence after an episode of anaphylaxis vs LLR and what effect does venom immunotherapy (VIT) have on this risk profile

Answer 9

The Apidae family (honey bees) and the Vespidae family (yellow jackets, yellow hornets, white-faced hornets, and paper wasps) belong to the order Hymenoptera and account for most of the stings that lead to anaphylactic reactions. The stings are usually painful. Children who have had a previous anaphylactic reaction have a 30% risk of recurrence. In Adults it can be up to 60%. VIT is safe and highly effective – reducing to risk to 5%. People with local reactions have a low risk of a future anaphylactic reaction. A family history does not put a child at increased risk – the risk of anaphylaxis is <1%. Venom specific IgE is not indicated because it is common to have a positive test but not to exhibit symptoms when exposed. Asymptomatic sensitisation may be >30%. There is no indication for testing as a positive result without a history of anaphylaxis does not predict future risk.

Question 10

What would cause a significantly elevated IgE (Normal: 0-35kIU/L)

Answer 10

Total IgE levels depend on size of organ affected with allergic sensitization

• Eczema > asthma > allergic rhinitis
• 50% of atopic patients will have a normal total IgE (poor correlation)

Question 11

Hereditary angioedema

Answer 11

Hereditary condition
1/10,000- 1/50,000

Type 1: C1-INH deficiency (low lvels and function) 85%
Type 2: normal or high C1INH, poor function - 15%
Type3: normal C1INH- rare

SERPING1 gene chromosome 1

• Autosomal dominance (25% de novo)
• Most heterozygotes
• Deletion/non-sense: Type 1 (deficiency)
• Mis-sense: Type 1 (dysfunction)

Type 3: mostly female, genetics unclear

Associated: SLE, Sjogren’s, IBD, coeliac, pancreatitis, depression

Recurrent angioedema without urticaria
- Skin: face, genitals, extremities (painful- worse in extremities for children, may precede respiratory attacks)
- Gastrointestinal: abdominal pain, distension, N&V, diarrhoea, may be only presentation- recurrent episodes of acute abdomen
- Respiratory: laryngeal swelling (+/- upper airway)
Peaks 24h resolves 48-72h
Frequency/severity depends on family history
50% will experience first episode before 10yrs
Increases around puberty

Often no trigger identified
Mechanical trauma- dental procedures/procedures requiring intubation
Stress
Infection
Hormonal changes (puberty, menstruation, OCP use- COCP, POP protective)

Investigate if clinical suspicion or positive FHx

• C4 (screening)- if low suspicion
• C1INH level & functional assay → 50% below normal range if positive, repeat testing before making definitive diagnosis (can have false low levels with processing on functional assay)
• Genetic testing: more useful for HAE type 2

Management (acute attacks)
Urgent management if laryngeal
Less urgent if mild cutaneous, GI

• Icatibant: bradykinin antagonist (known HAE patients >2y/o), S/C, weight based dosing, more available
• Berinert: C1 inhibitor concentrate- IV- hospital or home with training (20U/kg), use when incatibant ineffective, black box warning of thromboembolic events

May need prophylaxis if dental/intubation

• Berinert
• Icatibant
• Danazol

Consider longer term prophylaxis if significant impact on patient QOL
- Berinert