15. Allergy To Dental Materials + Drugs

Question 1

LOs

Answer 1

Question 2

allergen routes of entry

Answer 2

4 ROUTES OF ENTRY

• percutaneous/ mucosa
  ~ eg. plants / pet scratch
• injection
  ~ eg. bee stings
• inhalation
  ~ eg. hay fever (pollen) / asthma (dust)
• ingestion
  ~ eg. food (nuts) / medicine

Question 3

what is a allergic reaction vs toxic reaction?

• specific immune response?
• dose dependent?

Answer 3

ALLERGY
- an immunologically based sensitivity
* Specific immune response to the allergen
* Not dose dependent
* Reaction will change on subsequent exposure

TOXICITY
- a non-immunologically based reaction
* Non - specific, not immune
* Dose dependent
* May be accumulative
* Reaction will be similar on subsequent exposure

Question 4

1. what is hypersensitivity
2. classifications?

Answer 4

1
* state of altered reactivity
* body reacts with an exaggerated immune
response to a foreign substance

2
* Hypersensitivity reactions classified as:
~ immediate type I
~ delayed IV

Question 5

Type I hypersensitivity reaction

Answer 5

1. Antigen binds to specific IgE
2. IgE is bound to high affinity Fc receptors on mast cells
3. Cross linking between IgE / Fc receptor complex causes degranulation
   - release of histamine , serotonin , proteases , cytokines , leukotrienes
4. Chemical cascade attracts eosinophils , neutrophils and macrophages to site of antigen / antibody complex
5. Leukotrienes and histamines induce vascular permeability
   - causes smooth muscle contraction and bronchoconstriction

• extreme case = anaphylactic shock , wheezing

Question 6

Type III hypersensitivity reaction

Answer 6

• activation of complements
• activation of polymorphs
• antibody:antigen complex that occurs in circulation and settle down onto a cell membrane (particularly
  kidneys)

Question 7

Type IV hypersensitivity

Answer 7

• delayed type
• mediated by T cells (Th1, Th17, Tc)
• activated T cells secrete chemokines, cytokines
  (IFN-y, TNF)to recruit and activate macrophages
• activated macrophages secrete further proinflammatory cytokines (IL-12, TNF), tissue damage from degranulation
• formulation of granuloma: macrophages/ multinucleated giant cells, eosinophils, T cells, fibroblasts
• mechanism in organ-specific autoimmune disease
• not instantaneous

(TNF = tumour necrosing factor)

Question 8

what are the types of hypersensitivity and what do they do?

Answer 8

1. Type 1 – Immediate IgE mediated - Anaphylaxis
2. Type 2 – Auto antibody mediated
3. Type 3 – Immune complexes
4. Type 4 – T cell mediated - Delayed hypersensitivity

Question 9

Relevance of Allergy to Dentistry

Answer 9

Dental team
* Management + awareness of Anaphylaxis
* Contact dermatitis may affect staff

Patients
* Awareness of previous allergy
* Reduce exposure to potential allergens

Question 10

Materials used in dentistry that could cause problems

Answer 10

*Drugs
~ Local anaesthetics
~ cortico-steroids
~ antibiotics
~ analgesics

• Restorative materials
  ~ Amalgams
  ~ Ionomers
  ~ Composites
  ~ Metals & Porcelains
• Clinical materials
  ~ Latex
  ~ Impression materials
• Tooth paste/mouth washes

Question 11

what side effects can drugs cause on the oral mucosa

• Corticosteroids
• Methotrexate
• Gold
• Penecillamine
• Antimalarials
• NSAID’s

Answer 11

DRUGS SIDE EFFECTS
Corticosteroids candidosis
Methotrexate ulceration
Gold lichenoid reactions
Penecillamine loss of taste
Antimalarials lichenoid reactions
NSAID’s lichenoid reactions
(rarely), oral ulceration

Lichenoid reactions = white patches within the mouth that look like lichen planus

Question 12

what is this?
what drugs may cause it?

Answer 12

lichenoid reactions

• nifedipine
  ~ used for hypertension
• Salazopyrene
  ~ anti inflamm used in GI, reheumatology,
  dermatology

Question 13

what is this?
what drugs may cause it?

Answer 13

burn

• aspirin

Question 14

what is this?
what drugs may cause it?

Answer 14

gingival hyperplasia

• nifedipine
  ~ hypertensions

Question 15

oral reactions to toothpaste and mouthwashes

Answer 15

• Gingival desquamation (peeling)
• Gingival swelling & granulomatous (formed by T cell reactions) reactions
• Benign migratory glossitis
• Epithelial desquamation, inflammation
• Ulceration

Question 16

oral reactions to Creams, Ointments, Impression materials

Answer 16

• Contact stomatitis
• Gingival desquamation, swelling & granulomatous
  reactions
• Mucosal Swelling
• Epithelial desquamation, inflammation
• ulceration

Question 17

Adverse reactions to Local Anaesthetics (LEARN???)

Answer 17

• True allergy rare and accounts for <1% adverse
  reactions
• True allergy may be delayed as well as immediate
  type
• In UK 70 million dental LA given annually
• Adverse reactions to lignocaine & prilocaine
  preparations reported to CSM over 25 year period
  was 249 and included 9 deaths
• LA account for 5-10% of adverse reactions to
  anaesthetics drugs
• Adverse effects are
• Associated with blocking ion channels in cell
  membranes (CVS and CNS toxicity)
• Due to other effects of drug or vehicle (mainly
  peripheral nerve complications
• Allergic reactions (often a mistaken diagnosis)
• Mechanical or other effects of technique such as
  needle trauma or introduction of infection
• need to work out if was truly an allergic reaction or caused by something else

Question 18

Adverse reactions to Local Anaesthetics

reasons for referral to LA allergy testing clinics

(LEARN???)

Answer 18

• Collapse after LA (immediate or 2 hours later) (25%)
• Swelling of lips, eyes, cheeks, face (immediate and up to 2 hours later) (25%)
• Rash on chest, limbs, or contact area (1-7 hours later) (15%)
• Breathlessness, sweating, nausea, disorientation (10%)
• Headaches, irregular pulse and low BP.(8%)
• Swelling of throat, difficulty in breathing (8%)
• Behavioural changes (minutes to hours later) (5%)
• Sleepiness, dizzy (5%)

Question 19

Skin tests for type 1 local anaesthetic allergy

Answer 19

Stage 1 : prick test
- small amount of LA dropped onto arm
- skin is pierced with a small needle to introduce a small dose
- helpful for highly sensitive patients
- not good discriminators of allergy alone

Stage 2 : intradermal
- 25 micrometres of LA introduced underneath the skin
- causes white area around test site caused by vasoconstriction of LA
- more positive outcomes

Stage 3: intrabuccal test

Answer 20

Conclusions
* Scratch skin tests alone are not good discriminators of allergy, intradermal tests are better discriminators

• Prilocaine produced more positive skin reactions than any other local anaesthetic agent tested
• In 95 of the 100 patients referred with suspected
  anaphylactoid reactions to local anaesthetic agents, negative skin reactions to at least one of the agents allowed intrabuccal challenge and subsequent recommendation of an agent for future use
• Skin testing, though not providing formal proof of allergy, provides a useful test to indicate local anaesthetics which may be used for future procedures

Question 21

Type IV - hypersensitivity - contact hypersensitivity EGs to LA

Answer 21

• Contact sensitivity
• Mantoux skin test
• Homograft rejection
• involved in Orofacial granulomatosis (OFG)

Question 22

how to find out what particular products / chem constitutions someone is allergic to

Answer 22

patch testing

using aluminium wells

Patches left in place for 48 hours

Results are read at 48 and 96 hours

Patches with immediate sensitivity are removed

Question 23

What causes a lichenoid reaction on buccal mucosa ?

Answer 23

• lichenoid reaction to amalgam

Question 24

Reactions to Latex

Answer 24

• Dental school staff and students at high risk of sensitisation (Tarbo et al 1997)
• less common now as latex free gloves
• Skin sensitisation
  Dentists about 10%
  General hospital staff 5-8%
  Nurses 9%
  Anaesthetists 16%
• Sensitisation may worse in symptomatic asthmatics
• Percentages of new staff being sensitized will be less as no longer using powdered gloves

Question 25

Latex allergy - Management

Answer 25

Non latex gloves - plastic - polyvinyl Advise patients to carry non latex gloves with them Polyurethane condoms Latex policy in clinics Specific RAST test - skin scratch test with latex Blood test - check if IgE against latex is raised Antihistamines Epipen - extreme , contains adrenaline for anaphylactic shock

Question 26

Summary – Materials used in dentistry

Answer 26

* Medicines causing Anaphylaxis – covered in other lectures * Medicines causing Mucosal reactions * Local Anaesthetic reactions * Contact sensitivity to dental materials * Type 4 reaction * Patch testing * Latex

Question 27

causes of lip swelling

Answer 27

* Urticaria & Angioedema (specific fluid build up) * Reactions to Foods * Granulomatous conditions affecting the lips & oral cavity

Question 28

1. what is urticaria? 2. signs and symptoms? 3. how long does it clear away in?

Answer 28

* It sometimes occurs together with angioedema 1 Hives 2 * Wheals - spots or patches of raised red or white skin * Wheals are usually itchy, painful or cause a burning sensation 3 * Usually clear away in a few hours, and are then replaced by other fresh wheals.

Question 29

Angioedema 1. signs and symptoms 2. how long does it last?

Answer 29

* Often associated with autoimmune disease 1 * Angioedema is the name given to deeper swelling affecting the skin over the arms, legs, torso or face * May also affect the tongue, mouth, throat and sometimes the upper airway 2 * Swellings commonly last for more than 24hrs, and usually there is no itching

Question 30

Causes of Chronic Angioedema

Answer 30

* Food allergy (particularly nuts, shellfish, milk & eggs) * Oral Allergy Syndrome * Medicines * Antibiotics * Angiotensin –converting enzyme (ACE) Inhibitors - Enalopril, Lisinopril etc:) * Angiotensin-2- receptor blockers (ARBs) – Irbesartan, Losartan etc:) * Aspirin & NSAIDS * Beta blockers * Latex * Hereditary (C1 esterase inhibitor deficiency) ~ Attacks triggered by – stress / injury/ surgery / dental treatment / pregnancy / medications ~ Often not possible to identify cause of chronic angioedema * Associated with auto immune disease

Question 31

Oral Cavity Reactions to Foods

Answer 31

* Usually type 1 sometimes type IV * Oral cavity less sensitive than skin or nose * Peanuts most common. (? Does cracking of nuts break through protective mucin coat) * Other agents have been identified as causing problems * Octyl gallate antioxidant preservative - sore tongue & erythema (Pemberton et al) * Pumpkin seed -> swelling and Asthma (Fritsch et al)

Question 32

Immediate Food Allergy 1. what type of hypersensitivity reaction is it? 2. small or large quantity of food? 3. symptoms 4. how long does it take for reaction to develop? 5. diagnostic tests?

Answer 32

1 * Type I reaction - Anaphylaxis 2 * Small quantity food needed 3 * Perioral Erythema * Lip Swelling * Oral Itching * Tongue + pharyngeal swelling * Nausea + vomiting 4 * Reaction develops in minutes to hours 5 * Diagnostic skin tests available

Question 33

Food Allergy

Answer 33

* Immediate - Type I * Delayed o Does it really exist? - Coeliac disease + dermatitis herpetiformis well established = delayed hypersensitivity o Large quantity of food needed o Develops in hours and weeks o No diagnostic test except withdrawal & re- challenge

Question 34

Food intolerance

Answer 34

* Food intolerance (non-allergic hypersensitivity) is much more common o Onset of symptoms is usually slower and may be delayed by many hours after eating the offending food o Symptoms may also last for many hours, even into the next day o Intolerance to several foods or a group of foods is not uncommon, and it can be much more difficult to decide whether food intolerance is the cause of chronic illness, and which foods or substances may be responsible

Question 35

Symptoms of Delayed Food Allergy

Answer 35

* Eczema * Arthralgia * Poor concentration / headaches / depression * Irritable bowel syndrome / Crohn’s disease * Urinary frequency * Arthritis + rhinitis

Question 36

Oral Allergy Syndrome / Pollen Food Syndrome 1. cause? 2. who develops 3. type of hypersensitivity reaction

Answer 36

1 * Pollen allergens * Birch most common 2 * Adults develop > children * Usually occurs in people allergic to pollen from trees, grasses, weeds * Proteins of similar structure in fruit 3 * Distinctive type 1 reaction following direct contact of food and oral mucosa * Link to Orofacial granulomatosis patients?

Question 37

Oral Allergy Syndrome (OAS)

Answer 37

* Oral allergy syndrome (OAS) is a common food-related allergic condition that develops in adults. OAS is connected to environmental allergies, such as hay fever * Features of oral allergy include swelling of mouth, periorbital tissues, pharynx * Birch allergy strongest association * 20% of patients with OAS may be scratch positive to apples, peaches, kiwifruit, and rarely chestnut, salami * Specific allergen Bet vI identified in birch and apples * Most common foods usually apples, peaches, kiwi, hazelnuts & almonds * Antigens inactivated by cooking * Other pollen – food cross reactions * Latex – Fruit Syndrome (Avacado, Banana, Mango)

Question 38

oral facial granulomatosis causes

Answer 38

Question 39

SUMMARY

Answer 39

Urticaria & Angioedema * Causes of swelling around the face and mouth after dental treatment Food allergy * Immediate & Delayed * Oral Allergy syndrome

Question 40

Guidelines for the Management of these reactions

Answer 40

Establish provisional diagnosis: ~ Allergy, toxicity or physiological reaction ~ local anaesthetics, dental materials, food additives, mouthwash, toothpastes, etc * Previous history of reaction - mild/severe * Onset - rapid/delayed -how soon after contact * Type of symptoms - rash, oedema, conscious level, breathing difficulties, oral ulcers * Previous management of reaction - none/medication/hospitalisation

Question 41

how to test for hypersensitivity reactions?

Answer 41

Immediate (Type I) reactions * Allergy testing- scratch tests / intradermal / intrabuccal challenges * Serology ~ Mast Cell Tryptase Levels ~ Complement/C1 Esterase Inhibitor ~ Total IgE + Specific IgE (RAST tests) * Other Routine blood tests ~ FBP / B12 / Folate / Ferritin Delayed hypersensitivity (Type IV) * Allergy testing - Patch tests

Question 42

Complementary & Alternative Testing

Answer 42

* Leukocytotoxic Test * IgG Elisa Test (not IgE RAST test) * Applied kinesiology * VEGA testing (Electrodermal testing) * Hair analysis * Auriculo-cardiac reflex * Stools analysis for yeast & parasites

Question 43

Management of patients

Answer 43

* If allergy not proven with allergy testing, clear typed letter to referrer of findings and diagnosis. Always copy to GP * If allergy proven, give information to patient on proven allergens identified. Discharge from clinic with letter to referring GP/GDP * Consider advice such as avoidance of precipitating allergen (suggest alternatives if possible, for LA) * Use of MedicAlert badge * Prophylactic antihistamines/corticosteroids * Second generation non sedating – eg: Fexafenadine * Prednisolone 10mg for severe acute attacks * Availability of adrenaline (Epipen)/ emergency support services

Question 44

SUMMARY

Answer 44

*Mechanisms present in oral cavity for all types of allergic (hypersensitivity reactions) * Established examples in oral cavity ~ Type 1 (Peanut) ~ Type 2 (Pemphigus) ~ Type 3 (Herpes & Erythema Multiforme) ~ Type 4 (Lichenoid) *How to distinguish between allergy, toxicity and pharmacological reactions *What clinical / laboratory tests are helpfu

Question 45

Type II hypersensitivity reaction

Answer 45

- mediated by IgG binding to antigen on cell or tissue surface - IgG Fc binds to Fcy receptors of macrophages, NK (natural killer) cells - IgG Fc also activates complement - opsonisation and activation of phagocytic cells - degranulation or phagocytosis induces tissue damage - mechanism in organ-specific disease (self-antigen or tissue)