Immunodeficiency, hypersensitivity, autoimmunity oral reactions to drug therapy

1. Immunodeficiency, hypersensitivity, autoimmunity & oral reactions to drug therapy Dent 451 Lecture 13 Dr. Jumana Karasneh

2. Causes of Immunodeficiency Primary Intrinsic failure in development of one or more parts of immune system Hereditary Humoral Immunity X-linked Agammaglobulinemia Selective immunoglobulin deficiencies (IgA deficiency) Cellular Immunity DiGeorge Syndrome Secondary X-linked Agammaglobulinemia Defect in B cell function… NO IgA, IgM, IgD or IgE Severe recurrent bacterial infections Life span is decreased due to infections Immunoglobulin replacement therapy & antimicrobial Therapy Selective immunoglobulin deficiencies (IgA deficiency) Common disease IgA is absent Discovered only during adulthood due to chronic respiratory tract infection Although the only immunoglobulin secreted in saliva, NO effect on dental or periodontal disease X-linked Agammaglobulinemia Defect in B cell function… NO IgA, IgM, IgD or IgE Severe recurrent bacterial infections Life span is decreased due to infections Immunoglobulin replacement therapy & antimicrobial Therapy Selective immunoglobulin deficiencies (IgA deficiency) Common disease IgA is absent Discovered only during adulthood due to chronic respiratory tract infection Although the only immunoglobulin secreted in saliva, NO effect on dental or periodontal disease

3. Causes of Immunodeficiency Primary Secondary Extrinsic influences that modify / suppress part of immune system Infections (HIV, TB) Drug Induced Immunosuppressant (Cyclosporine, Corticosteroids) Chemotherapy Malnutrition (a major cause world wide) Malignancy (Leukemia, Lymphoma) Diabetes

4. An overactive (exaggerated) response to antigens upon second contact after the host has been sensitized Four Types of Hypersensitivity Reactions: Type I (Anaphylactic) Reactions Type II (Cytotoxic) Reactions Type III (Immune Complex) Reactions Type IV (Cell-Mediated) Reactions Hypersensitivity (Allergy)

5. Type I Hypersensitivity Occurs immediately (within minutes) after second exposure to Ag. Histamine increase dilation & permeability of blood vessels + constriction of smooth muscles. Anaphylaxis

6. Hypersensitivity disease Urticaria & Angioedema Cause: Food Drugs (penicillin, ACE, NSAID) Insect bite Natural rubber latex Pathogenesis: Type I hypersensitivity Dilatation of blood vessels in superficial connective tissue Urticaria Dilatation of blood vessels in Deep connective tissue Angioedema

7. Hypersensitivity disease Urticaria & Angioedema Clinical Picture: Urticaria: red well-demarcated area + itching Angiodema: diffuse swelling of normal color.

8. Hypersensitivity disease Urticaria & Angioedema Complication: Angioedema in Larynx/Pharynx? asphyxiation. Treatment: Remove the cause if known. Anti-histamine-main stay epinephrine in emergency

9. Cells destruction caused by binding of IgM, IgG antibodies to cell surface antigen ABO blood group system Rh blood group system Rh- people are sensitized to destroy Rh+ blood cells Hemolytic disease of newborn Type II (Cytotoxic) Reactions Hemolytic disease of newborn: Fetal cells are destroyed by maternal anti-Rh antibodies that cross the placentaHemolytic disease of newborn: Fetal cells are destroyed by maternal anti-Rh antibodies that cross the placenta

10. IgG & IgM antibodies attacking soluble antigens immune complexes deposited in organs activate complement inflammatory damage. Glomerulonephritis: Inflammatory kidney damage (SLE) Type III (Immune Complex) Reactions

12. Type IV (Cell Mediated) Reactions(delayed hypersensitivity)

13. Delayed hypersensitivityContact mucositis & dermatitis Cause: Direct contact of an allergen (topical drugs, acrylics, metal based alloys, flavoring, gloves) with skin/mucosa Affects only area with direct contact with allergin

14. Delayed hypersensitivityContact Dermatitis

15. Delayed hypersensitivityContact Mucositis Less common than dermatitis: Saliva washes Ag before penetrating oral mucosa Higher vascularity than skin ? Ag is removed before recognition Antigens include Toothpaste, mouthwashes Flavorings: cinnamon, peppermint Dental material: monomer in acrylic, nickel, mercury

16. Delayed hypersensitivityContact mucositis & dermatitis Diagnosis: Patch test Treatment: - removal of allergen - corticosteroids

17. How can you identify patients at higher risk of allergic reaction Atopic patients (eczema, allergic rhinitis, asthma, …) patients taking multiple medications Medically compromised patients

18. Angioedema Causes: Allergic : type I hypersensitivity Idiopathic Hereditary ? C1 esterase inhibitor deficiency

19. Hereditary C1 esterase inhibitor deficiency Autosomal dominant genetic disease ? family history Some cases are acquired (isolated mutation ? no family history All mucosa might be affected ? abdominal pain, difficulty breathing

20. Hereditary C1 esterase inhibitor deficiency Treatment: Synthetic androgen (Danazol corrects the underlying biochemical deficiency by increasing serum concentrations of the deficient C1 esterase inhibitor) Fresh frozen plasma of C1 esterase in emergency

21. Autoimmunity Immune response is directed against the host’s own tissues Cell mediated Humoral Examples: Pernicious anaemia Immunobullous diseases Sjogren’s syndrome

22. Oral Diseases With Immunologic Pathogenesis Immune-mediated disease. Recurrent aphthous ulcers. Lichen Planus (LP). Hypersensitivity disease. Urticaria & Angiodema Contact mucositis & dermatitis. Erythema multiforme. Autoimmune disease. Sjogren syndrome. Systemic Lupus Erythematosus (SLE). Pemphigus & Pemphigoid. Immunodeficiency disease. AIDS

23. Oral reaction to drug therapy Oral ulceration Lichenoid drug eruptions Localized reaction to topical therapy Discoloration of oral mucosa Erythema multiforme Lupus erythematosus Angioedma Fixed drug eruption Xerostomia (reduced salivary flow) Mucositis

24. Mucositis Induced by: systemic medication Gold salts NSAIDs Chemotherapy Radiotherapy Pt might be on medication for long time before developing mucosistis

25. Oral reactions to antibiotics Allergic reaction Angioneurotic oedema Vesicle formation Management: Depends on severity Stop medication and warning of further use Antihistamines Adrenaline with steroid in emergency

26. Oral reactions to antibiotics Black hairy tongue Follows systemic antibiotics Usually return to normal after cessation of drug NOTE: use of antibiotic MW does not induce fungal infection ? no need to combine antifungal with antibiotics MW

27. Oral reactions to steroid Acute erythematous candidosis Acute / chronic pseudomembranous candidosis NOTE: use of topical steroid induces fungal infection ? must combine antifungal with topical steroid

28. Instructions for patients on steroids Use topical antifungal as long as fungal infection is present (repeated many times) Miconazol gel is more tolerated in case of ulcerative conditions treated by steroids Systemic antifungal for resistant cases Rinse mouth after steroid inhaler Use of spacer device

29. Drug therapy and periodontal tissues Drugs inducing gingival enlargement: Phenytoin (50%) Ciclosporin Calcium channel blockers (10-15%) Oral contraceptive pills ?

30. Phenytoin Anticonvulsant Affect 50% of pt Chronic fibrotic enlargements Management: Change medication? Strict oral hygiene gingivectomy

31. Ciclosporin Immunosuppresive Widely used in renal transplants

32. Fixed drug eruptions Delayed typed hypersensitvity reaction? Mainly skin lesion, rarely mucosa is involved Start as vesicle/ bulla ? ulcer Drug induced (salicylates, dapsone, tetracyclines, sulfonamides) Appear at the same site (fixed) whenever the drug is initiated

33. The End :o)