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11 Angioedema Rapid onset increase in vascular permeability resulting in swelling in the subdermis and submucosa Face, tongue, larynx, abdomen, arms and legs Variable speed of onset. Can be very fast. Airway is at risk

12 Angioedema Histamine Mast Cell Degranulation Robust allergic reaction insect bites foods medications Antihistamines Corticosteroids epinephrine Bradykinin Genetic Autoimmune disorder C1 esterase inhibitor deficiency Uncontrolled activation of the complement system ACE inhibitors Lymphoproliferative disorder C1 esterase inhibitors (icatibant) Fresh frozen plasma

17 Juvenile Idiopathic Arthritis Heterogenous group of conditions, often seronegative Unknown cause, genetic polymorphisms result in abnormalites in both the innate and adaptive immune systems. 1/1000 Generally children between 6 and 16 years F>M 40% have TMJ involvement Early treatment important to prevent deformity and growth abnormality

20 Systemic Lupus Erythematosus - Lupus Multisystem disease, varies in severity and prognosis Disease of women of childbearing age, Asian and African American Multiple body systems affected Arthralgia, fever, chest pain, oral ulcers, lymphadenopathy, rash, anemia Cause unknown. Genetic. Environmental Antinuclear antibodies ANA + Low levels of complement

21 Systemic Lupus Erythematosus - Lupus Constitutional symptoms Rash Mucosal Ulcers Inflammatory polyarthritis Photosensitivity Serositis Nephritis Athersclerosis Anemia Leukopenia Thrombocytopenia Subdermal-mucosal inflammation Direct immunofluorescense (IgM, IgG or C3 ANA 95% Anti DNA

22 Systemic Lupus Erythematosus Lupus Oral Ulcers Typical Discoid Lesions with white halo

23 Treating Oral Ulcers in Lupus Ulcers may correlate with active disease or drug reaction. Buccal mucosa, palate and lower lip. Biopsies should be carried out. Treat with intralesional or topical steroid.

28 Started treating patient at 14. Multiple consults. Unconfirmed Diagnosis Age 28 seroconverts. ANA +. Diagnosis of Lupus Multiple Surgeries TMJ, Hips, Shoulders, Knees,

29 2008. One year post revision of TMJ replacement

30 year post further TMJ revision Multiple surgeries other joints Near fatal Serotonin Syndrome post surgery

31 Systemic Lupus Erythematosus - Lupus Treatment to control disease DMARDS Avoid sunlight Significant increased risk of cardiovascular disease and shortened life span

32 Scleroderma Non-inflammatory small vessel vasculopathy and fibrosis Dense Collagen deposited in the tissues of the body. F/M 4/1 5 th and 6 th decades Skin and Multiple systems affected Poor Prognosis with caridiac involvement.

33 Scleroderma Microstomia, Perioral tissues very tight, submucosal fibrosis, gingival recession. Stiff tongue TMJ fibrosis and trismus oral access challenging for dental care. Can be treated successfully with implants

36 Sjogren s Syndrome Autoimmune inflammation that progressively destroys the secretory glands of the body. Dry mouth, skin, cough, dry eye. Primary Sjogrens Syndrome caused by a combination of genetic and ennvoronmental triggers (infection). Secondary Sjogrens Syndrome caused by other autoimmune diseases.

37 Sjogren s Syndrome Female/male - 10 /1 Estrogen humoral and cellular immunity Microchimerism Viral proteins Engulfed molecules Degraded self structures Biopsy, ANA, HLAs, RF, ESR, Salivary flow Lymphocytes

38 Sjogren s Syndrome- Dental Considerations Xerostomia Dental Caries Poor denture retention Oral Hygiene Fluoride Salagen 5 mg.qid (asthma, pulmonary disease, CHF) Oral lubricants (Biotene, Oracoat) Dental Implants

39 Mixed Connective Tissue Disorder Overlap Syndromes Syndromes with features of 2 Connective Tissue Disorders 40 to 60% evolve into Scleroderma or SLE Raynaud s Syndrome a common feature Can cause pulmonary hypertension and death

40 Scleroderma and Sjogren s Syndrome

42 Inflammatory Arthritis and Sjogren s Disease

44 SLE and Scleroderma 18 years post TMJ TJR

46 Lupus, Scleroderma, Sjogren s, Crohn s Disease One year post TMJ TJR

47 Inflammatory Diseases of Muscle Inflammatory Myopathies Heterogenous group of muscle diseases, Polymyalgia, Dermatopolymyalgia with skin lesions Proximal muscle weakness and pain (hip and shoulder) Autoimmune lymphocytic process cause muscle fibre destruction Can occur in association with other autoimmune CTD like SLE, RA, Scleroderma Genetic and environmental risk factors Myositis specific autoantibodies Cell mediated, humoral autoimmune and nonimmune mechanisms damage muscle fibres Crippling if untreated

48 Inflammatory Diseases of Muscle Inflammatory Myopathies Diagnosis is based on lab, EMG and muscle biopsies Treatment is drug and physiotherapy (exerecise) based. glucocorticoids immunosuppressive drugs cytotoxic drugs like Imuran, cyclosporin Few recover normal function - methotrexate Surveillance for malignancy

49 Fibromyalgia NOT an autoimmune disease!! Included in this lecture because common mimicker of inflammatory polymyalgias commonly present as a TMD patient treatment is very different

50 Fibromyalgia Widespread Chronic Myalgia 2% of the population Female/Male 9/1 With other chronic disorders Irritable bowel TMD Chronic Fatigue Tension Headache Disruptive sleep Pelvic Pain

51 Fibromyalgia Greater than 3 months duration Bilateral Diagnosis of exclusion, relies on patient reporting 11/18 painful sites, 4 kg of load with palpation Centrally maintained or amplified pain, deficiency in pain inhibitory pathways. Frequently comorbid with other rheumatological diseases

52 Fibromyalgia Management, not treatment as there is no known cure for this chronic condition. Multimodal. Pharmacology, physiotherapy, exercise, biofeedback, TMDs are a common component of Fibromyalgia.

53 Fibromyalgia Disordered sensory processing widespread allodynia widespread hyperalgesia Genetic vulnerability associated with polymorphisms in genes associated with pain transmission, neurotransmitter and stress response pathways.

54 Education and self management Exercise Cognitive behavioral therapy Pharmacological antidepressants mixed reuptake inhibition of serotonin and NE duloxetine (Effexor) (Pristiq) antiseizure drugs gabapentin, lyrica cannabinoids Opioids and NSAIDs prove to not be useful for centrally mediated pain

55 Treat comorbid causes of pain. classic non- surgical treatment modalities for concommittant TMDs

56 Seronegative Spondyloarthropathies Ankylosing spondylitis Reactive arthritis Psoriatic arthritis HLA-B27+ RF- ANA- Peripheral arthritis, Spondyloarthitis refers to the spine

57 Ankylosing Spondylitis Inflammatory, Progressive arthritis Axial Skeleton.4 1.6%, m/f 10/1 Hereditary Frequently involves the TMJ

58 Ankylosing Spondylitis Glucocorticoids NSAIDS DMARDS Exercise to prevent neck fusion TMJ affected Oral appliances are effective Do well with Total Joint Replacement

59 Ankylosing Spondylitis

60 Psoriatic Arthritis 1 2% 5 10% have arthritis 50% involve TMJ m/f = 1/ Arthritis can be severe and destructive Genetic, infective T lymphocyte mediated keratinocyte proliferation

System, University of Toronto Centre for Excellence in

65 Total TMJ Replacement Surgery in Patients With Autoimmune TMJ Destructive Arthropathy Sinai Health System, University of Toronto Centre for Excellence in TMJ Reconstructive Surgery Since patients 1100 joint replacements

66 Preoperative Diagnosis Ankyl. Spond. 3% Pierre Robin Seq. 1% Pathology 7% Condylar Resorption 10% Condylar hyperplasia 1% Rheumatoid Arthritis 7% DJD 59% Ankylosis 12%

67 Patient Age Sex (M/F) Diagnostic System Number of joints Pre-op ROM (mm) (T1) Post-op ROM (mm) (1 year)(t2) Last post-op ROM (mm)(t3) Pre-op pain (T1) Post-op pain (T3) Mean follow-up (months) 1 27 F RA Biomet /10 0/ F AS Biomet /10 0/ M AS Biomet 2 0 No data 20 0/10 0/ M AS Biomet /10 0/ F RA Biomet /10 0/ F JRA Biomet /10 0/ F RA Biomet /10 Neuropathic pain 7/ M JRA Biomet /10 0/ F RA Biomet /10 3/ F RA TMJ/Concepts /10 0/ F RA TMJ/Concepts 2 35 No data 40 0/10 0/ M JRA Biomet /10 0/ F JRA Biomet /10 0/ F AS Biomet /10 0/ F Lupus Biomet 2 13 No data 20 7/10 4/ F JRA TMJ/Concepts /10 7/ F PA Biomet 2 0 No data 15 3/10 0/ F PA Biomet /10 0/ M RA TMJ/Concepts /10 0/ M PA Biomet 2 20 No data 32 7/10 No data F Lupus Biomet 1 No data No data No data F RA Biomet /10 0/ F RA TMJ/Concepts /10 No data F Lupus Biomet /10 3/ F PA Biomet /10 8/ F RA Biomet 1 35 No data No data 7/10 No data No data

68 Preoperative Diagnosis Number of Patients (n) Number of Joints Rheumatoid Arthritis (2 unilateral) Psoriatic Arthritis 4 8 Ankylosing Spondylitis 4 7(1 unilateral) Juvenile Idiopathic Arthritis 5 10 Lupus 3 5 (1 Unilateral) Total 35 66

69 Preoperative Pain VAS Score Postoperative Pain Last Follow up VAS Score Mean Standard Deviation Total 33 26

70 Preoperative ROM In mm (T1) Postoperative ROM in mm (T2) Postoperative ROM in mm, last follow up Mean Standard Deviation Total Patients

71 Autoimmune Arthro-myopathies and Dentistry Abnormal Connective Tissue Biology. Healing and disease resistance impaired. Drugs used for treatment impair healing, oral biology (salivation), the immune system and resistance to infection. The TMJ can be affected along with other joints. Access for oral hygiene, dental treatment, pain.

72 Autoimmune Arthro-myopathies and Dentistry Oral hygiene, home fluoride Heightened vigilance for caries and periodontal disease Consultation with rheumatologist Drug holiday OR optimal timing for oral surgery Antibiotics. NO PENICILLINS IN PATIENTS ON METHOTREXATE!!!! Heightened vigilance for infection

73 Autoimmune Arthro-myopathies and Dentistry Affecting the TMJ Oral Appliances Physiotherapy NSAIDS and Muscle Relaxants in consultation with Rheumatologist Oral and Maxillofacial Surgery referral glucocorticoid injection arthroscopic surgery Total Joint Replacement for destroyed joints Concomitant Orthognathic Surgery for secondary malocclusion

74 Autoimmune Myo-arthropathies Summary Joint growth and development Normal joint anatomy and biology The Immune system, innate and adaptive, humoral and cellular Autoimmune disease etiology and pathogenesis seropositive and seronegative myoarthropathies treatment DMARDs Autoimmune Disease and Dentistry.

75 Thank You! David J. Psutka DDS, FRCD(C)

Kelley's Textbook of Rheumatology. 2 Volume Set. Text with Internet Access Code for Premium Consult Edition

Kelley's Textbook of Rheumatology. 2 Volume Set. Text with Internet Access Code for Premium Consult Edition Firestein, G ISBN-13: 9781437717389 Table of Contents VOLUME I STRUCTURE AND FUNCTION OF BONE,