COURSE TITLE: COURSE INSTRUCTOR: COURSE CREDITS: Autoimmune Diseases: Systemic and Oral Health Considerations JoAnn R. Gurenlian, RDH, PhD and Ann Eshenaur Spolarich, RDH, PhD 2 CEUs COURSE DATE: August 1, 2012 COURSE DESCRIPTION: Approximately 2% of the population suffers from autoimmune disease and most of these individuals are women. The diseases themselves, as well as the medication management, can adversely affect the oral cavity and significantly impact quality of life. This course will highlight common autoimmune diseases, oral and systemic disease manifestations, and appropriate dental hygiene interventions. LEARNING OBJECTIVES: Upon completion of this continuing education course, the participant will be able to: 1. Describe the pathophysiology of immune system dysfunction. 2. Identify common signs and symptoms of various autoimmune diseases. 3. Discuss the classes of drugs that are frequently used to treat autoimmune diseases. 4. Identify oral manifestations of common autoimmune diseases. 5. Recognize the adverse oral and systemic complications associated with medications used to treat autoimmune diseases. 6. Discuss the effects of chronic steroid use on the human body. 7. Identify important practice management considerations when planning dental hygiene care for patients with autoimmune disease. 8. Deliver dental hygiene services safely and effectively for patients with autoimmune disease. *This material is the intellectual property of the authors and may not be reproduced or distributed without their written permission. 1
CASE STUDY #1 Ruth Burkowski is a 43 year old female who presents with a complicated medical history. She was diagnosed two years ago with Systemic Lupus Erythematosis (SLE( and Rheumatoid Arthritis (RA). It took almost 3 years to diagnose her SLE condition. She has a family history of CVD and arthritis. Her father died of a pulmonary infection and her mother of TB. Her older brother died of brain cancer, and her younger brother has a history of Sjögren s Syndrome. She states that her mother told her she had an allergic reaction to penicillin as a child, but she has no recollection of this episode as she was very young when it occurred. Ruth is presently under the care of a rheumatologist who coordinates her medical treatment with a cardiologist and an endocrinologist. She attends regular dental hygiene appointments every 3 months and has a significant dental history of caries, episodic gingivitis, and fractured teeth requiring both endodontic and restorative treatment. Identify the significant aspects of Ruth s medical and dental history. What follow-up questions would you ask Ruth? What are symptoms of RA? What are symptoms of SLE? What are the oral signs of SLE? What medications are used to treat these conditions? What are the side effects of these medications? 2
DRUGS FOR AUTOIMMUNE DISEASE MANAGEMENT RHEUMATOID ARTHRITIS IS THE PHARMACOLOGIC MODEL: Goals of therapy are palliative o Reduce joint inflammation and swelling o Relieve pain and stiffness o Encourage normal function Aspirin and NSAIDS are cornerstones of treatment o Reduce inflammation (swelling), pain and fever Adverse Effects of Aspirin o Adverse gastrointestinal effects Ulceration and bleeding o Effects on the kidney Retention of sodium and water May cause hyperkalemia and edema in some patients o Special senses adverse effects Tinnitus is sign of toxicity to aspirin Requires decrease in dose o Respiratory system Toxic levels may cause central respiratory paralysis = respiratory acidosis NSAIDS o ibuprofen (Motrin, Advil, Rufen, Nuprin) o naproxen (Naprosyn, Aleve) o sulindac (Clinoril) o tolmetin (Tolectin) o fenoprofen (Nalfon) o piroxicam (Feldene) o diclofenac (Voltaren) o flurbiprofen (Ansaid) o diflunisal (Dolobid) o etodolac (Lodine) o nabumetone (Relafen) Oral Complications of Aspirin and NSAIDS o Prolonged bleeding Usually not clinically significant Control with local hemostatic agents as needed o Oral aphthous ulceration/aphthous stomatitis 3
sulfasalazine (Azulfidine) Salicylate: 5-aminosalicylic acid Interferes with prostaglandin synthesis Used for treatment of RA in patients with inadequate response to aspirin and NSAIDS Side effects: headache, photosensitivity, GI distress, anorexia COX-2 Inhibitors = celebrex (Celecoxib) Contraindicated in aspirin/nsaid allergic patients (cross-sensitivity) Celebrex is contraindicated in those allergic to sulfonamides Multiple drug interactions OK to use with low dose aspirin Adverse cardiovascular risks: o Increased risk for stroke o Monitor patient s blood pressure when used with antihypertensives = decrease effectiveness of BP meds o Increased risk for heart attack Unanticipated bleeding may occur o Assess bleeding times when used with warfarin DMARDS = Disease-modifying anti-rheumatic drugs *Also known as SAARDS = slow-acting Used for treatment of RA and OA Potential to reduce or prevent joint damage Used for patients who do not respond to COX-2 inhibitors Slow course of disease = may induce remission Prevent further destruction of joints/tissues Slow onset of action o May take 3 to 4 months to see effects Preparations (subfamilies of DMARDS): o Immune modulators methotrexate, leflunomide Anticytokine therapies etanercept, infliximab, adalimumab, anakinra o Antimalarials Chloroquine, hydroxychloroquine o Penicillamine o Gold compounds 4
IMMUNE MODULATORS *methotrexate (Rheumatrex, Trexall) = also used for chemotherapy Used alone or in combination with other DMARDS *Drug of choice for severe RA or psoriatic arthritis (especially when unresponsive to NSAIDS) Slows appearance of new erosions within involved joints Response within 3-6 weeks of starting treatment o Faster effect than other DMARDS Adverse effects of methotrexate: o Dose is lower than for chemotherapy, so fewer side effects o Most common: mucosal ulcerations, nausea o Side effects with chronic use: Cytopenias depression of WBC count Cirrhosis of liver Acute pneumonia-like syndrome leflunomide (Arava) Mechanism: anti-proliferative and anti-inflammatory effects Reduces pain and inflammation Slows progression of structural damage Adverse Effects of leflunomide (Arava) o Most common: headache, diarrhea, nausea o Other: Weight loss Allergic reactions Flu-like syndrome Skin rach Alopecia Hypokalemia Teratogenic = contraindicated in pregnant women and women of child-bearing years Hepatotoxic ANTICYTOKINE THERAPIES Interleukin-1b and tumor necrosis factor alpha are proinflammatory cytokines involved in pathogenesis of RA When secreted by synovial macrophages, IL-1b and TNF alpha stimulate synovial cells to proliferate and synthesize collagenase, which degrades cartilage, stimulates bone resorption and inhibits proteoglycan synthesis Drug antagonists (blockers) to these cytokines are effective in treating RA 5
etanercept (Enbrel) TNF alpha blocker o Binds to TNF molecules and blocks interaction with cell surface receptors Indicated for moderate to severe RA May affect defenses against infections and malignancies Risk for activation of hepatitis and tuberculosis in carriers Given subcutaneously Side effects: headache, injection site reaction, upper respiratory tract infections infliximab (Remicade) TNF alpha blocker Inhibits progression of structural damage and improves physical function in patients with moderate to severe disease Long-term use is associated with developing antibodies against the drug, unless the drug is combined with methotrexate Side effects: infections leading to pneumonia, cellulitis; blood dyscrasias adalimumab (Humira) TNF alpha blocker o Recombinant monoclonal antibody that binds to TNF alpha receptor sites Treatment of moderate to severe RA in patients with inadequate response to one or more DMARDS Decreases signs and symptoms, and structural damage Subcutaneous administration only Side effects: headache, nausea, rash, injection site reaction anakinra (Kineret) Interleukin-1 receptor antagonist (blocker) Treatment of moderate to severe RA in patients who have failed one or more DMARDS Slows degradation of cartilage and bone loss Side effects: headache, injection site reaction, infections ANTIMALARIALS Preparations: chloroquine (Aralen); hydroxychloroquine (Plaquenil) Treatment of RA that is unresponsive to NSAIDS o May be used in combination with aspirin and/or corticosteroids Slow progression of erosive bone lesions May induce remission 6
Severe side effects/toxicity: o severe eye damage o *blue-black intraoral pigmentation CHELATING AGENT penicillamine (also used as antidote for heavy metal poisoning) Slows the progression of bone destruction and RA Mechanism: depresses circulating IgM rheumatoid factor, depresses T-cell activity Used for RA treatment after gold salts have failed, but before use of corticosteroids Side effects: dermatologic, nephritis, aplastic anemia Oral Complications with Penicillamine o Infection o Delayed healing o Prolonged bleeding o Oral ulcerations GOLD COMPOUNDS Decrease inflammation Slows progression of bone and articular destruction Mechanism: (exact is unknown) o Taken up by macrophages causing inhibition of phagocytosis and lysosomal membrane stabilization o Decreased serum rheumatoid factor o Alterations in immunoglobulins o Decreased complement activation o Inhibition of prostaglandin synthesis o Decreased lysosomal enzyme activity Preparations: expensive to buy and administer o aurothioglucose o auranofin (Ridaura) o gold sodium thiomalate (Aurolate) High incidence of toxicity = requires intensive monitoring o Dermatitis with mucosal ulcerations o Proteinuria o Neutropenia o Thrombocytopenia Oral Complications with Gold o Infection o Delayed healing 7
o Prolonged bleeding o Glossitis o Aphthous stomatitis o Blue-black intraoral pigmentation IMMUNOSUPPRESSIVE DRUGS Used in cases of refractory RA o azathioprine (Imuran, Azasan) o cyclophosphamide (Cytoxan) o cyclosporine (Sandimmune, Gengraf, Neoral, Restasis) azathioprine (Imuran, Azasan) Immunosuppressant Also an antineoplastic drug for cancer therapy Used also in dentistry with prednisone for severe erosive lichen planus, major aphthous stomatitis, erythema multiforme, benign mucous membrane pemphigoid Side effects: fever, malaise, alopecia, rash, GI, blood dyscrasias, hepatotoxic cyclophosphamide (Cytoxan) Immunosuppressant Also an antineoplastic drug for cancer therapy Used for severe RA Side effects: alopecia, infertility, GI, blood dyscrasias cyclosporine (Sandimmune, Gengraf, Neoral, Restasis) Immunosuppressant Used primarily to prevent rejection of organ transplants Used for severe active RA that is not responsive to methotrexate Inhibition of production and release of interleukin II and inhibits interleukin IIinduced activation of resting T lymphocytes Side effects: o Headache, hypertension, hirsuitism, GI, tremor, renal toxicity, gingival hyperplasia ( <16% of users) CORTICOSTEROIDS Synthetic Glucocorticoid Medications Indicated for: o Autoimmune diseases o Immunosuppressive therapy in organ transplant patients o Respiratory disease management o In dentistry: For reduction of pain and swelling Treatment of inflammatory pathologies of oral mucosa 8
Potency Each steroid is rated as to potency as compared to a hydrocortisone equivalent dose The more potent the drug: o the lower the dose o the higher the risk for adrenal suppression Topical applications least likely to cause adrenal suppression (except those with high potency) Systemic steroids more likely to cause adrenal suppression Compound Potency Equivalent Dose (mg) Short-Acting < 12 hours Cortisol 1 20 Cortisone 0.8 25 Intermediate-Acting 12-36 hours Prednisone 4 5 Prednisolone 4 5 Methylprednisolone 5 4 Triamcinolone 5 4 Long-Acting > 36 hours Paramethasone 10 2 Betamethasone 25 0.75 Bexamethasone 25 0.75 Dosing Considerations with Steroids Drugs are taken in the morning Alternate day therapy Lengthening interval between dosing allows for same effects with fewer side effects Adrenal gland functions normally on off day HPA axis not suppressed; less risk for adrenal suppression Alternate day therapy is used for patients who must take steroids for longer than 1 month 9
Dosing Considerations with Steroids Daily therapy poses greater risk for adrenal suppression Chronic steroid users wean off steroids in descending doses (tapered dosing) Normal adrenal output of cortisol = 20-30 mg hydrocortisone equivalent Any medication dosage that exceeds this amount may cause suppression During stress, adrenals may secrete up to 300 mg of hydrocortisone equivalent DETERMINING NEED FOR STERIOD SUPPLEMENTATION Patients with past history of steroid use Medical history interview Determine if steroids used within past 2 weeks Reason for stopping? (previous indication) Type, dose and duration of therapy Look for signs/symptoms of adrenal insufficiency Identify dental treatment needs Routine dental care No supplementation necessary Major invasive oral surgical procedure Physician consultation, Laboratory testing Patients Currently Taking Steroids Medical history interview Dose and duration of systemic steroid use Identify signs/symptoms of possible insufficiency For diagnostic and minimally invasive procedures: Patient takes usual daily dose Schedule patient first thing in morning Stress reduction protocol Pain control Anxiety control Monitor blood pressure For major invasive procedures (oral surgery) Physician consultation Laboratory testing Steroid supplementation as needed Steroid Supplementation in Dentistry Routine dental procedures (excluding extractions) Patients currently taking steroids None Use good pain and anxiety control 10
Patients with history of regular steroid use none Patients using topical or inhaled steroids none Complications of Chronic Steroid Use Insomnia Peptic ulceration (watch NSAIDS) Osteoporosis Cataract formation Glaucoma Growth suppression Delayed wound healing Oral Side Effects of Steroid Use Candidiasis = most common Patients using inhalers Use topical antifungal therapy Poor wound healing = long-term use Masking of oral infections = anti-inflammatory Xerostomia = inhaled and systemic steroids Power-assisted devices Fluorides SUGGESTED RESOURCES Little JW, Falace DA, Miller CS, Rhodus NL. Dental Management of the Medically Compromised Patient. 7 th ed. St. Louis: Mosby Elsevier, 2008. Pickett FA, Terezhalmy GT. Dental Drug Reference with Clinical Implications. 2 nd ed. Baltimore, Lippincott Williams & Wilkens, 2008. Wynn RL, Meiller TF, Crossley HL. Drug Information Handbook in Dentistry. 17 th ed. Hudson, Lexi-Comp Inc., 2011. 11