3Recurrent aphthous stomatitis (RAS) painful oral ulcers and recurring conditionmay involve buccal, labial, tongue, hard and soft palate mucosal surfaces.Shallow ulcers covered by gray, yellow or white plaques with erythema.
4RAS (Aetiology&Treatment) Unknown aetiology: possible genetic predispositionSome factors local trauma, stress, local infections, food allergy,hormonal fluctuations, exposure to chemicals.In association with systemic diseases including HIV infection,Behcet’s disease, inflammatory bowel disease and celiacTreatment:topical corticosteroidsClorhexidine gluconate mouthwash decrease the severity ofepisodeMore severe conditions immunosuppressive therapy
5Benign Migratory Glossitis (BMG) Affects 2% of populationpsoriasisUnknown aetiologyIrregular dekeratinized desquamated papillae (red in color), surrounded by elevated whitish or yellow margins due to hyperkeratosis.Neutrophil migration into epithelial layer
6Oral Lichen Planus (OLP) Chronic inflammatory conditionAffects 2 % of population.Unknown aetiologyHyperkeratosis: appearingmostly as white slightly raised lines and/or erythema, erosions
7OLP (Pathogenesis&Treatment) T cell mediated autoimmune disease: cytotoxic T cellinduced apoptosis of epithelial cells.Lichenoid lesions:include lichenoid drug reactions (anti-hypertensive agents,NSAID, anti-malarials).In association with systemic diseases:autoimmune liver disease, chronic active hepatitisand hepatitis C virus infection, graft versus host diseaseTreatment: topical/systemic steroids
8Mucous membrane pemphigoid (MMP) Autoimmune vesiculobullous disease affects mainly oral mucosa, ocular involvementIg and complements deposit along basement membraneDestruction of hemidesmosomes, Nikolsky’s sign, mucosa separates from underlying connective tissueTreatment: topical / systemic steroidsIn severe conditions immunosupp therapy
9Behçet’s disease A rare autoimmune disease T cell mediated auto-inflammation of blood vessels.Triple-symptom complex: recurrent oral aphthous ulcers, genital ulcers, and uveitis.Non-scarring oral lesions in the form of aphthous ulcersSystemic involvement of visceral organs such as GIS, pulmonary, musculoskeletal, cardiovascular and neurological systems.Treatment: easing the symptoms, reducing inflammation and controlling immune system.high dose steroids/ immunesupp therapy
10Pharmaceuticals agents in Oral medicine Anaesthetics/analgesics (palliative medicine)Anti-inflammatory agentsAnti-viral,Anti-fungal agentsLocal/systemic corticosteroidsImmunomodulatory/immunosuppressive
11Palliative medicine -symptomatic treatment relieve symptoms without having a curative effect on the underlying disease or causereduce pain and uncomforthelp to enhance the quality of life
14Anti-viral agents Treatment of herpes infection Acyclovir: local/systemic treatmentValacyclovir: prodrug of acyclovirBetter bioavailabilitySystemic treatmentFor treatment of severe viral infections otherwise palliative treatment.
15Anti-fungal agents Candida albicans infections Nystatin/Mycostatin Toxic for parenteral useOral suspension, creamMikanazolOral gel, suspension/creamFlukonazolSystemic treatment (oral or iv)
16Corticosteroidsnaturally produced in adrenal cortex: mineralocorticoids (aldosterone) and glucocorticoids (cortisol)involved in physiological processes:Stress response,Immune response,Anti-inflammatory,Fat and protein metabolism
17Production of cortisol by adrenal glands about mg/day mostly in the morning,Only 5 % is active others bound to serum proteins.produce x10 when needed.Extra cortisol helps body to cope with stress such as infection, trauma, surgery, or emotional problems.When the stressful situation ends, adrenal hormone production returns to normal.
18Release of cortisolThe paraventricular nucleus (PVN) a neuronal nucleus in hypothalamus activated by stressful and/or physiological changesHPA axis: hypothalamic-pituitary-adrenal axis
21Mechanism of actionenter cells where they combine with steroid receptors in cytoplasmIn nucleus controls synthesis of proteins, including enzymes that regulate cell activitiesControl over a wide range of metabolic functions including inflammation
22Corticosteroid Drugs Include: Short actingt1/2 < 12 hIntermediateactingt1/ hlong actingt1/2 > 36 h
23Corticosteroids in Oral medicine Most of the cases intermediate-acting topical steroids.Clobetasol propionate0.05 % oral gel or oral pasteTriamcinolone (0.1 % oral paste)Systemic treatment with prednisolone in severe cases
24Clobetasol propionate analogue of prednisolonein skin disorders such as eczema, psoriasis and autoimmune diseases like lichen planus.anti-inflammatorytopical corticosteroids, cream and ointment forms; high range of potencyrecommended to use <2 weeks,not exceed 50 mg/week (risk to suppress HPA axis)
25Immune homeostasis or Autoimmunity Regulatory T cells (Treg, Tr1)Pathogenic T effector cells(TH1, TH17, TFH)antigen+Genetic background (MHC, non-MHC genes)+ environmental factors (smoking, infection,..)antigenAutoimmunityRegulatory T cells(Treg, Tr1) suppressionPathogenic T effector cells(TH1, TH17, TFH)Dysregulation of the adaptive immune system lies at the core of autoimmune and immune-mediated disease pathogenesis.Hyperactivation of self-antigen– or microbial antigen–specific effector T and B cells, defects in the regulation of adaptive immune system, result in thebreakdown of immune homeostasis and the development of immune-mediated diseases. As a result, the mechanisms by which effector and regulatory adaptive immune cells are dysregulated is still under research.Major histocompability complex (MHC), is protein molecules, which are degraded proteins in the cell and expressed on the cell surface of the cell as an antigen (self or non self proteins) mediate interaction of leukocytes, also called human leukocyte antigen (HLA).
271) Immunosuppressive agents Cyclosporine/TacrolimusImmunosupp, inhibit T cell activity by inhibiting the transcription and release of IL-2 and proinf cytokines.Mech of action: they diffuse into T-lymphocytes and block calcineurine activity –an enzyme responsible for IL-2 transcription.Have no effect on antigen recognition by T cells.for treatment of RA, psoriasis, severe atopic dermatitis and in organ transplantation to prevent rejection.Tacrolimus is a makrolid ab. Its mechanism of action is similar to cyclosporine. Tacrolimus is more potent than cyclos so lower doses are required.
282) Anti-proliferative, cytotoxic agents AzathioprineIt is a prodrug and converted to active metabolite in the bodyimmunosuppressive, DNA synt inibition mainly effects T and B cellsadverse effects: carcinogenic; bone marrow suppression.Therefore Myophenolate mofetil is increasingly used in place of azathioprine
292) Anti-proliferative, cytotoxic agents Mycophenolate mofetil (MMF):less toxic alternative to azathioprine,Selective cytotoxic agent for T and B cells,Mech action: blocks the production of guanosine nucleotides required for DNA synthesis.supresses lymphocyte prolif. and ab production by B cellsin transplant medicine, autoimmune disease
302) Anti-proliferative, cytotoxic agents MethotrexateIn treatment of autoimmune diseasesAt high doses: toxic effect on rapidly dividing cells (malignant, myeloid, gastrointestinal and oral mucosa). Therefore as a chemotherapy agent.Mech: inhibits metabolism of folic acid. Folic acid is needed for the de novo synthesis of the nucleoside thymidine, required for DNA synthesis. It overall inhibits the synthesis of DNA, RNA, and proteins.At low doses: immunosupp effect by inhibiting T cell activation.
313) Cytokine modulatorsanti-TNF-α antibodies (infliximab, adalimumab, etarnecept)By binding TNF-α neutralise biological activity and inhibit its proinf. effectssuppress adhesion mol. expressiondecrease IL-6 and IL-1 levelsUsed in autoimmune diseasesAdverse effects: increase risk for infections, hypersensitivity reactions, blood disordersexpensive
32antigenAntigen presented lymphocytes are activated and produce IL-2 and thereby proliferation of Th cells. Th1 cells control macrophage initiated responses and responsible for the release of inflam. cytokines (TNF alpha and IL-1). Th1 response and TNF alpha and IL-1 have roles in the pathogenesis of number of chronic inflam. diseases like RA. IL-4 stimulates proliferation of Th2 cells to B cells and later to plasma cells (produce ab). Th2 responses predominate in allergic conditions like eczema. Organ rejections involves both Th1 and Th2 responses.
33Other agents Dapsone: anti-bacterial effect inhibits neutrophil functions such as chemotaxis, oxidant productionIrreversible inhibition of MPOColchicine ( a plant poison): anti-inf drugBlocks COX-2 and prostaglandin synthesisMitosis inhibiting functionInhibition of neutrophil chemotaxis and mild cytokine modulationCombination therapy with dapsone for treatment of acute attacks of autoimmun dis like, Behcet’s
34Other agents Hydroxychloroquine: antimalarial drug has immunmodulatory propertiesdiminish the formation of peptide-MHC protein complexes required to stimulate T cells and result in down-regulation of the immune responsesuppress neutrophil functions + inhibits IL-1, TNF alphaeffective in treatment of lichen planus and some other autoimmune dis.
35References Clinical Oral Medicine and Pathology. Jean M. Bruch, Nathaniel Simon Treister (e-book).Immunotherapy in 2020 Visions and Trends for Targeting Inflammatory Disease. A. Radbruch, H.-D. Volk, K. Asadullah, W.-D. Doecke (e-book).Medical Pharmacology at a Glance. Neal, Michael (e-book).Immunopharmacology. Manzoor M. KhanISBN: (e-book.)