Hypersensitivity in Dental Practice

• Hypersensitivity is:

  • Immune-mediated antigen-specific reactions that are inappropriate or excessive and result in harm to the host
  • Antibody-mediated
  • T-cell mediated
  • Hypersensitivity reactions can occur against
  • Environmental agents
  • Self-antigens
  • Infectious agents eg hep B, leprosy (tuberculoid reactions)
• Type of hypersensitivity: immediate hypersensitivity (type I)

  • Pathologic immune mechanisms: IgE antibody
  • Mechanisms of tissue injury and disease: mast cells and their mediators (vascoactive amines, lipid mediators, cytokines)
• Type of hypersensitivity: antibody mediated (type II)

  • Pathologic immune mechanisms: IgM, IgG antibodies against cell surface or extracellular matrix antigens
  • Mechanisms of tissue injury and disease: opsonisation and phagocytosis of cells. Complement- and Fc receptor-mediated recruitment and activation of leukocytes (neutrophils, macrophages). Abnormalities in cellular functions, e.g. Hormone receptor signalling.
• Type of hypersensitivity: immune complex mediated (type III)

  • Pathologic immune mechanisms: immune complexes of circulating antigens and IgM or IgG antibodies
  • Mechanisms of tissue injury and disease: Complement- and Fc receptor-mediated recruitment and activation of leukocytes (neutrophils, macrophages).
• Type of hypersensitivity: T cell mediated (type IV)

  • Pathologic immune mechanisms:
  • CD4+ T cells (delayed-type hypersensitivity)
  • CD8+ CTLs (T cell-mediated cytolysis)
  • Mechanisms of tissue injury and disease:
  • Macrophage activation, cytokine-mediated inflammation
  • Direct target cell killing, cytokine-mediated inflammation
• Allergy:

  • Increasing rapidly
  • 30% teenagers in UK have asthma
  • 1-2% true food allergy increased to 10% in some studies
  • Hygiene hypothesis
  • Decreased infection
  • Increased immunisation
  • Microbiome
  • Genetics important atopy trait
  • Preferential switch from type 1 profile to type 2 profile i.e excess of Il-4, Il-5 and Il-13
• Environmental agents:

  • Characteristics of environmental agents that make it easy for the body to mount an allergic response:
  • Small particles
  • Lung, skin, eye, gut, mouth
  • Aeroallergens (pollens, housed dust mite, moulds, fungi)
  • Foods - nuts, shellfish, milk, egg, wheat
  • Drugs
  • Venom
  • Risks of severe allergic reactions are variable (some reactions may be worse than others - unpredictable)
• Classification of hypersensitivity (allergic) reactions:

  • Type 1 (frequently equated with term allergy)
  • IgE-mediated degranulation of mast cells and basophils
  • IgE is produced and coats the surface of the mast cells
  • When the allergen then binds to the IgE, the mast cell is activated
  • This causes a release of histamine, heparin, lysosomal enzymes and proteases
  • This is what causes the symptoms of an allergic reaction
• Clinical consequences of allergy:

  • Urticaria (hives) & angioedema (swelling)
  • Capillary permeability - reduced blood pressure, hypovolaemic shock
  • Smooth muscle contraction
  • Airways
  • GI
  • Bladder
• Diagnosis of type I hypersensitivity:

  • History:
  • Ask whether people develop symptoms that we'd expect to see in an allergic reaction: rhinitis (runny nose), conjunctivitis (itchy, sore eyes), wheezing, urticaria, angioedema, and anaphylaxis (collapsing, vomiting, diarrhoea)
  • Rapid onset of symptoms after exposure
  • Recurrence on re-exposure
  • Seasonality (pollens)
  • Resolution with allergen avoidance
• Diagnosis of type I hypersensitivity:

  • Investigations:
  • Skin prick tests
  • Blood tests
  • Measure specific IgE to the allergen you wish to know the positive or negative result to (false positive and negative results)
  • Challenge tests
  • Oral/IV
  • Open
  • Double blind placebo controlled (neither patient nor doctor know on what day the allergen is being given so that symptoms can be assessed without bias)
  • Bronchial

  
• Immediate type reactions and anaphylaxis due to dental products:

  • Latex
  • Comes from milky sap of Hevea brasiliensi
  • Risk factors for latex allergy include:
  • Atopy (asthma, eczema, hay fever)
  • Regular exposure
  • Spina bifida or myelomeningocele
• Latex allergy - history:

  • Ask if they've had any symptoms when blowing up balloons, using condoms, or wearing rubber gloves
  • Latex Fruit allergy syndrome (people with latex allergy also have problems with banana, kiwi fruit, avocado, pineapple, chestnut, tomato, potato, lettuce, cannabis)
• Latex allergy - diagnosis:

  • Skin prick tests - investigation of choice
  • Specific IgE - less sensitive/specific
  • Challenge tests
  • Difficult to standardise
  • Potential for allergic reactions
• Latex in dental practice: latex gloves, latex dam, gutta percha, some prophylaxis cups, mixing bowls, orthodontic elastics, suction tips, bite blocks, amalgam carriers, IV tubing, emergency resus masks, BP cuffs, bungs in IV drugs, protective eyewear, elastic bands & pens.
• Latex allergy - management protocol should be available:

  • Staff awareness
  • First on the list
  • No powdered latex gloves
  • Wipe down all surfaces
  • No latex containing equipment to be used
  • Emergency drugs and equipment should be latex-free

  Staff should be aware of risks both to them and to patients - latex free gloves if possible.
• Immediate type reactions and anaphylaxis due to dental products:

  • Formaldehyde
  • Disinfectant for root canal treatment
  • Local anaesthetic
  • Extremely uncommon
  • Adverse reaction in 0.5% of all dental LAs administered
  • Reactions usually vasovagal, tachycardia or apparent collapse
  • Latex from latex-stopped vials, preservatives
  • Chlorhexidine
• Type 1 reaction to local anaesthetics:

  • Refer for skin prick tests
  • Allergy to esters (procaine, benzocaine) more common than amides (lidocaine, prilocaine, articaine, bupivicaine)
  • Cross-reactivity between esters (frequent) and amides (less frequent)
  • Use preservative-free solutions if in doubt. (Sulphites may also be present as a reducing agent - can exacerbate some asthmatic patients)
• Immediate type reactions and anaphylaxis due to dental products:

  • Antibiotic allergy
  • Commonest is penicillin family
  • IgE-mediated can occur
  • Both agent-specific and family directed
  • Cephalosporin allergy occurs in 15%
  • Allergy to gentamicin, erythromycin and metronidazole are uncommon
  • Skin prick tests, specific IgE and challenge
• Treatment of anaphylaxis:

  • UK resuscitation council guidelines
  • Definition of anaphylaxis:
  • Severe allergic reaction with 1 or both of:
  • Breathing difficulties
  • Hypotension
• Potential causes of angioedema:

  • Allergic reaction
  • C1 inhibitor deficiency
  • (Idiopathic angioedema/medication related)
• Treatment of Type 1 reactions:

  • Antihistamines
  • Cetirizine, Loratidine, Acravastine, (Chlorpheniramine), Fexofenadine
  • Steroids
  • Prednisolone, Hydrocortisone
  • Bronchodilators
  • Salbutamol

  
• C1 esterase deficiency:

  • Recurrent deep swelling with minor trauma, stress, oestrogens
  • Recurrent abdominal pain
  • Can have fatal laryngeal oedema
  • No urticaria
  • Autosomal dominant - therefore runs in families
  • Low C4
  • Treatment of acute attacks is replacement of the enzyme
  • Long-term treatment is with androgenic steroids and tranexamic acid
  • Before any dental treatment DISCUSS WITH IMMUNOLOGY DEPARTMENT
  • Premedication with C1-esterase-inhibitor concentrate

  
• Other potential mechanisms of action in dental practice:

  • Type: I
  • Mechanism: IgE
  • Time: seconds/minutes
  • Example: angioedema
• Other potential mechanisms of action in dental practice:

  • Type: II
  • Mechanism: cytotoxic
  • Time:
  • Example: transfusion treatment
• Other potential mechanisms of action in dental practice:

  • Type: III
  • Mechanism: immune complex
  • Time: 6-8 hours
  • Example: serum sickness
• Other potential mechanisms of action in dental practice:

  • Type: IV
  • Mechanism: cell-mediated
  • Time: 48 hours
  • Example: contact dermatitis
• Potential allergens and irritants:

  • Antiseptics and hygiene products (mouthwash, toothpaste)
  • Impression materials
  • LA (type I and IV hypersensitivity reactions recognised)
  • Cements
  • Metals
  • Mercury, tin, silver, copper, gold alloys (silver, copper, platinum, pallidum, zinc), silver-pallidum alloys (zinc & copper), cobalt, chromium, molybdenum, beryllium & zinc
  • Rubber products
  • Resins/acrylates
  • Composites for fillings, bonding agents & dentures
  • Others
  • Initiator (benzoyl peroxide)
  • Inhibitor (hydroquinone)
  • Plasticiser (dibutylphthalate)
  • Pigments, dyes, nylon fibre & titanium/zinc oxides
• Presentation of allergic reactions:

  • Stomatitis
  • Lichenoid changes
  • Cheilitis and lip swelling
  • Facial swelling
• Oral lichenoid reactions/oral lichen planus:

  • Soreness in mouth/oral ulceration
  • Causes
  • Medications - antimalarials, NSAIDs, oral hypoglycaemics, and others
  • Infections
  • Possible type IV hypersensitivity to metals, nickel, resins, acrylates
  • Buccal mucosa, tongue, floor of mouth
  • Patch testing might be helpful
• Oral lichenoid reactions/oral lichen planus:

  • Type IV hypersensitivity to metals
  • Mercury most common
  • Gold
  • Cobalt
  • Tin
  • Silver
  • Palladium
  • Chromium
  • Patch tests:
  • Diagnosis
  • Patch tests to metals
  • Read at 48 hours, 4, 7 and 10 days for mercury hypersensitivity
  • Positive results:

  
• Oral lichenoid reactions/oral lichen planus:

  • Type IV hypersensitivity to metals - management
  • Removal of amalgam
  • Cessation of drug
  • Local steroid
  • (Removal of amalgam even when patch testing negative)
• Burning Mouth Syndrome:

  • Difficult
  • Most wear dentures
  • Iron or folate deficiency
  • Candida infection
  • Mostly NOT allergy - patch testing negative
  • If signs then NOT burning mouth syndrome
• Chelitis and lip swelling:

  • Inflammatory eruption
  • Causes
  • Irritancy e.g. Lip lick (36%)
  • Contact allergy (25%) lip cosmetics, toothpaste, dental materials, food (children), nail varnish, rubber gloves, metals, fragrance
  • Atopic dermatitis (19%)
• Chronic facial eruptions:

  • Intra-oral metal
  • Palladium
  • Chronic swelling
  • Gold
  • Facial dermatitis, soreness & oral lichenoid reactions
  • Pts may be patch test positive without symptoms
  • Nickel
  • Dermatitis or exacerbation of dermatitis usually around mouth
  • But in 16 patients known to be nickel allergic, crowns or bridges containing 66% nickel - no symptoms
• Allergy in dental practice is not common, but can be severe.

  • Type 1 - immediate
  • Urticaria, angioedema, wheeze, hypotension
  • Skin prick tests
  • Type 4 - delayed
  • Contact dermatitis/red mouth/lichenoid reactions
  • Patch tests
  • If suspicious, refer with symptoms of:
  • Type 1 allergy (e.g. To latex) to Immunology
  • Type 4 allergy (e.g. Metals) to Dermatology