Autoimmune Diseases PDF

2Q AUTOIMMUNE DISEASES Angela Chi, DMD [email protected] taking photos or video recording during this live class session is not permitted LEARNING OBJECTIVES Define and subclassify autoimmune diseases....

2Q AUTOIMMUNE DISEASES Angela Chi, DMD [email protected] taking photos or video recording during this live class session is not permitted LEARNING OBJECTIVES Define and subclassify autoimmune diseases. Discuss the epidemiology, etiopathogenesis, clinical features, differential diagnosis, microscopic/laboratory test features, treatment, and prognosis of autoimmune diseases (esp. those with oral, head and neck manifestations). Discuss the differential diagnosis for: “lichenoid” lesions diffuse oral pigmentation  AUTOIMMUNITY Immune reactions against self antigens  AUTOIMMUNE DISEASES Classification: Systemic vs. organ-specific Main disease mechanism: Autoantibody production Self-reactive T-cell activation Uncertain (but postulated to be autoimmune) MAIN MECHANISM SYSTEMIC ORGAN-SPECIFIC MEDIATED BY Systemic lupus Graves disease AUTOANTIBODIES erythematosus, pernicious anemia pemphigus, pemphigoid, acute rheumatic fever MEDIATED BY T CELLS Rheumatoid arthritis, Type 1 diabetes mellitus systemic sclerosis/ CREST, Sjögren syndrome POSTULATED TO BE IgG4-related disease Inflammatory bowel AUTOIMMUNE disease (Crohn disease, ulcerative colitis)  ETIOPATHOGENESIS OF AUTOIMMUNITY Fig 5.17 Kumar, Vinay, et al. Robbins & Kumar Basic Pathology. Available from: VitalSource Bookshelf, (11th Edition). Elsevier Health Sciences (US)  LUPUS ERYTHEMATOSUS Multisystem autoimmune dz >1.5 million individuals affected in the U.S.  Lupus Erythematosus 3 major forms Systemic (SLE) Chronic cutaneous (CCLE) (“discoid”) Subacute cutaneous (SCLE) Injury caused by autoantibodies to various tissue types and immune complex deposition IFANA erythematosus  I P Systemic Lupus Erythematosus F>M L Average age at diagnosis 31 yrs Nonspecific early Fever, weight loss, fatigue, malaise, arthritis Malar butterfly rash (~ 50% ) 033 https://commons.wikimedia.org/wiki/File:Lupusfoto.jpg; Doktorinternet, CC BY-SA 4.0 , via Wikimedia Commons  Systemic Lupus Erythematosus Kidney (40 -50% pts.) Cardiac Pericarditis Libman-Sacks endocarditis Pleuritis lungFascialayers Arthritis Hemolytic anemia, thrombocytopenia, lymphocytopenia, neutropenia FIG 5.26 Kumar, Vinay, et al. Robbins Basic Pathology E-Book. Available from: VitalSource Bookshelf, (10th Edition). Elsevier Limited (UK), 2017.  Discoid (Chronic Cutaneous) Lupus Erythematosus Elizabeth E. Cooper, Catherine E. Pisano, Samantha C. Shapiro, "Cutaneous Manifestations of “Lupus”: Systemic Lupus Erythematosus and Beyond", International Journal of Rheumatology, vol. 2021, Article ID 6610509, 19 pages, 2021. https://doi.org/10.1155/2021/6610509 https://creativecommons.org/licenses/by/4.0/ Little / no systemic involvement Scaly, erythematous patches or plaques Esp. w/ sun exposure https://dermnetnz.org/topics/discoid-lupus- erythematosus/; https://creativecommons.org/licenses/by-nc- nd/3.0/nz/legalcode McDaniel B, Sukumaran S, Koritala T, et al. Discoid Lupus Erythematosus. [Updated 2021 Jul 31]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK493145/ Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/)  Discoid Lupus Erythematosus atrophy, scarring and hypo- or hyperpigmentation Scalypatche Elizabeth E. Cooper, Catherine E. Pisano, Samantha C. Shapiro, "Cutaneous Manifestations of “Lupus”: Systemic Lupus Erythematosus and Beyond", International Journal of Rheumatology, vol. 2021, Article ID 6610509, 19 pages, 2021. https://doi.org/10.1155/2021/6610 509 https://creativecommons.org/licenses/by/4.0/ https://dermnetnz.org/topics/cutaneous-lupus-e rythematosus https://creativecommons.org/licenses/by-nc-nd/3.0/nz/legalcode  Lupus Erythematosus Oral May appear lichenoid or nonspecific In discoid LE: usually concurrent skin lesions Dermnet; https://dermnetnz.org/topics/discoid-lupus-e rythematos us/ https://creativecommons.org/licenses/by- nc-nd/3.0/nz/legalcode LUPUS CHEILITIS Dermatology Image Atlas https://www.dermis.net/dermisroot/en/1197 397/image.htm Table 16.5 Neville B et al. Oral and Maxillofacial Pathology. Available from: VitalSource Bookshelf, (5th Edition). Elsevier Health Sciences (US).  Autoantibodies cause damage directly or via immune complex deposition SKIN/MUCOSA: INTERFACE CHANGE FIG 5.21 Kumar, Vinay, et al. Robbins Basic Pathology E-Book. Available GLOMERULONEPHRITIS from: VitalSource Bookshelf, (10th FIG 12,11 Kumar, Vinay, et al. Robbins Basic Pathology E-Book. Available from: Edition). Elsevier Limited (UK) DIF: SHAGGY IgG DEPOSITION BMZ VitalSource Bookshelf, (11th Edition). Elsevier Limited (UK),  Lupus Erythematosus Tx: Avoid sun exposure Mild: NSAIDs/antimalarials, topical steroids Severe: systemic immunosuppressive tx  Lupus Erythematosus Px: SLE 20-yr survival: 75% CCLE better px, remission possible but may transform into SLE Differential diagnosis for “lichenoid” lesions Lichen planus Lichenoid drug eruption Lichenoid reaction to amalgam Chronic ulcerative stomatitis Lupus erythematosus Graft-versus-host disease Lichenoid dysplasia  RnF ACPA prunedasshole A cranky RESRACRP RHEUMATOID ARTHRITIS bothmarkers inflammati of Chronic inflammatory autoimmune disorder Mainly attacks joints (also skin, heart, blood vessels, lungs) ~1% of U.S. population activated CD4 T helper in Flamm RHEUMATOID ARTHRITIS F>M Genetic and environmental factors Activated CD4+ T helper cells release cytokines to activate inflammatory cells, synovial cells, fibroblasts, chondrocytes Destruction of articular bone and cartilage Fig 19.34 Kumar V. et al. Robbins Basic Pathology E-Book. Available from: VitalSource Bookshelf, 11th Edition). Elsevier Limited  RHEUMATOID ARTHRITIS Fatigue, weakness, https://www.physio- pedia.com/File:RA_Hand_1.png; Creative Commons Attribution- Share Alike 3.0 Unported license joint and muscle aches Joints: Symmetrical involvement (esp. hands, feet, knees, elbows) (TMJ 75%) Swelling, stiffness (esp. >1 hr morning), deformity  RHEUMATOID ARTHRITIS Joints: Pannus (inflamed synovium/fibrous tissue erodes cartilage/bone) Advanced dz: fibrous or bony ankylosis Fig 19.35 and 37 Kumar V. et al. Robbins Basic Pathology E-Book. Available from: PANNUS Synovial hypertrophy w/villi VitalSource Bookshelf, (11th Edition). Elsevier Limited (UK)  RHEUMATOID ARTHRITIS specifically Labs: more RhF, ACPA (anti-citrullinated protein antibodies) Increased ESR and C-reactive protein Tx: ESR CRP Immunosuppressants (corticosteroids, methotrexate, TNF antagonists, antimalarials) NSAIDs  RHEUMATOID ARTHRITIS Dental tx considerations: Upright chair position / short appointments / joint supports Immunosuppressive agents and BM suppression / adrenal suppression OH and limited dexterity TMJ pain, swelling, stiffness  stenosis Mitral value Children ACUTE RHEUMATIC FEVER 4Abeta hemolytic strep acute multisystem immune-mediated dz induced by group A beta-hemolytic streptococcal infection Ab’s to streptococcal cell wall antigens cross-react w/ host proteins (heart, joints)  ACUTE RHEUMATIC FEVER Esp. children Develops 2 to 3 wks after initial infection Fever, carditis, migratory polyarthritis, skin rash (erythema marginatum), Syndenham chorea https://www.myupchar.com/en, CC BY-SA 4.0 , via Wikimedia Commons https://commons.wikimedia.org/wiki/File:Depiction_of_a_child_suffe ring_from_ Rheumatic_Fever.png  RHEUMATIC HEART DISEASE FIG 9.19 Kumar, Vinay, et al. Robbins Basic Pathology E-Book. Available from: VitalSource Bookshelf, (11th Edition). Elsevier Limited (UK) MITRAL VALVE VEGETATIONS MITRAL VALVE STENOSIS (chronic / scarring)  RHEUMATIC HEART DISEASE Historical note: no longer an indication for antibiotic prophylaxis prior to dental treatment for prevention of infective endocarditis  anti topoisomerase 50170 🐭 Anti 🐭 antibodies acroosteolitis SYSTEMIC SCLEROSIS (“scleroderma”) Raynauds fingers Ulcer fingers sclero dactyly dense collagen deposition & microvascular injury skin/mucosal/organ involvement resorption of ramus angle  Systemic Sclerosis F>M Smooth, hard skin texture Mouse-like facies Labs: anti-Scl 70 (antitopoisomerase I) antibodies Panchbhai A, Pawar S, Barad A, Kazi Z. Review of orofacial considerations of systemic sclerosis or scleroderma with report of analysis of 3 cases. Indian Journal of Dentistry. 2016 Sep;7(3):134-139. DOI: 10.4103/0975-962x.186702. PMID: 27795648; PMCID: PMC501556 Creative Commons Attribution-NonCommercial- ShareAlike 3.0 License4.  Systemic Sclerosis https://commons.wikimedia.org/wiki/File:Raynaud_phenomenon.jpg Tcal at English Wikipedia, CC BY-SA 3.0 , via Wikimedia Commons RAYNAUD PHENOMENON  Systemic Sclerosis SCLERODACTYLY DIGITAL ULCERS and ACRO-OSTEOLYSIS https://dermnetnz.org/topics/skin-signs-of-rhe umatic- Srivastava R, Jyoti B, Bihari M, Pradhan S. Progressive systemic sclerosis with intraoral manifestations: A case report disease https://creativecommons.org/licenses/by-nc-nd/3.0/nz/legalcode, and review. Indian Journal of Dentistry. 2016 Apr-Jun;7(2):99-104. DOI: 10.4103/0975-962x.184645. PMID: 27433054; PMCID: PMC4934096. Creative Commons License  Systemic Sclerosis Resorption of ramus and angle of mandible Jagadish, Rekha & Mehta, Dhoom & Jagadish, P. (2012). Oral and periodontal manifestations associated with systemic sclerosis: A case series and review. Journal of Indian Society of Periodontology. 16. 271-4. 10.4103/0972-124X.99275. Creative Commons Attribution-NonCommercial-ShareA like 3.0 Unported GENERALIZED PDL SPACE WIDENING Systemic Sclerosis Crincoli, V.; Fatone, L.; Fanelli, M.; Rotolo, R.P.; Chialà, A.; Favia, G.; Lapadula, G. Orofacial Manifestations and Temporomandibular Disorders of Systemic Scleroderma: An Observational Study. Int. J. Mol. Sci. 2016, 17, 1189. https://doi.org/10.3390/ijms17071189Creative Commons Attribution (CC-BY) license (http://creativecommons.org/licenses /by/4.0/). MICROSTOMIA  Systemic Sclerosis Tx: (penicillamine, corticosteroids) Raynaud’s: calcium channel blockers, avoid cold & smoking Dental tx: microstomiaoral hygiene difficult Px: poor -- pulmonary / renal/ cardiac complications Sharma, Aditi & Arora, Pallak & Wazir, Sartaj. (2013). Hinged and sectional complete dentures for restricted mouth opening: A case report and review. Contemporary clinical dentistry. 4. 74- 7. 10.4103/0976-237X.111597. https://creativecommons.org/licenses/by-nc-sa/3.0/  CREST SYNDROME mild variant of limited systemic sclerosis anti-centromere antibodies  Calcinosis cutis Raynaud’s phenomenon Esophageal dysfunction Sclerodactyly Telangiectasia https://dermnetnz.org/topics/calcinosis-cutis; https://creativecommons.org/licenses/by-nc-nd/3.0/nz/legalcode https://dermnetnz.org/topics/skin-signs-of-rheumatic- disease https://creativecommons.org/licenses/by-nc- nd/3.0/nz/legalcode Bunn BK, van Zyl AW, Rahman L, van Heerden WFP. Oral medicine case book 62: CREST syndrome. S. Afr. dent. j. [Internet]. 2014 [cited 2021 Sep 30] ; 69( 7 ): 324-325. Available from: http://www.scielo.org.za/scielo.php?script=sci_artte xt&pid=S0011- 85162014000700005&lng=en. https://creativecommons.org/licenses/by-nc/4.0/deed.en TELANGIECTASIAS  Gg4 Sjögren Syndrome chronic autoimmune disorder involves salivary & lacrimal glands  Sjögren Syndrome NOTE: WE WILL DISCUSS THIS CONDITION IN MORE DETAIL DURING XEROPHTHALMIA NEXT WEEK’S SESSION ON XEROSTOMIA XEROSTOMIA https://commons.wikimedia.org/wiki/File:Sjogrens_Syndrome.jpg Scientific Animations, CC BY-SA 4.0 , via Wikimedia Commons  IgG4-RELATED DISEASE Newly described fibro-inflammatory disorder Autoimmune? Allergic? Elevated serum IgG4; IgG4-positive plasma cells; lymphocytes; fibrosis; and obliterative phelbitis  IgG4-RELATED DISEASE Esp. middle-aged to older M Submandibular glands, lacrimal glands, bile duct, thyroid, pancreas, kidneys, lungs, etc. Takano K et al. Auris Nasus Larynx 44:7-17, 2017. Creative Commons CC-BY-NC-ND license Tx: systemic steroids FIG 5.30 Kumar, Vinay, et al. Robbins Basic Pathology E-Book. Available from: VitalSource Bookshelf, (10th Edition). Elsevier Limited (UK), 2017.  I is hyperthyroidism T4 I I s TSH GRAVES DISEASE Autoantibodies targeting TSH receptors  hyperthyroidism  GRAVES DISEASE F>M, peak 3rd to 4th decades Ho, Yo & Chung, Eun & Park, Sin-Ae. (2014). A 3-year-old girl with Graves' disease with literature review. Annals of pediatric endocrinology & metabolism. 19. 154-8. 10.6065/apem.2014.19.3.154. Clinical features: https://creativecommons.org/licenses/by-nc/3.0/ Nervousness Heart palpitations Tachycardia Heat intolerance, sweating Weight loss Exophthalmos bulging Dermopathy eyes Labs: T4 elevated, TSH depressed TX: radioactive iodine, methimazole https://commons.wikimedia.org/wiki/File:Proptosis_and_lid_ retraction_from_Graves%27_ Disease.jpg Jonathan Trobe, M.D. - University of Michigan Kellogg Eye Center, CC BY 3.0 , via Wikimedia Commons  Graves Disease Dental considerations? Infection, trauma, surgical procedures may bring on thyrotoxic crisis (“storm”) Early: N/V, restlessness, abdominal pain Fever, sweating, tachycardia, Arrhythmia, pulmonary edema, CHF, coma, hypotension, death 20% mortality  DIABETES MELLITUS ~9.3% U.S. population defects in insulin secretion and/or action  TYPE 1 (5 to 10%) TYPE 2 (90 to 95%) PATHO- Breakdown in self-tolerance in T Insulin resistance in GENESIS cells to pancreatic β islet cell peripheral tissues & antigens  deficiency in insulin failure of compensation secretion by β cells; obesity- associated factors GENETICS Linked to MHC Class I and II genes No HLA linkage; candidate diabetogenic & obesity-related genes CLINICAL Onset often in Onset usually in FEATURES childhood/adolescence adulthood NL weight or weight loss prior to dx Most patients obese Circulating islet autoantibodies No islet autoantibodies similar long-term complications  DIABETES MELLITUS Damage to multiple tissue types (kidneys, eyes, nerves, blood vessels) Macrovascular dz atherosclerosis, MI, CHF, CVA, gangrene of feet Microvascular dz: Diabetic nephropathy (leading cause of Fig 14.5 Little, James, W. et al. Dental Management of the Medically Compromised Patient - E- Book. Available from: VitalSource Bookshelf, (9th Edition). Elsevier Health Sciences (US), 2017. end-stage renal dz in U.S.) Diabetic retinopathy Diabetic neuropathy (esp. extremities) Impaired wound healing Impaired resistance to bacterial & fungal infections Fig 20.32 Kumar V, et al. Robbins Basic Pathology E-Book. Available from: VitalSource Bookshelf, (10th Edition). Elsevier Limited (UK), 2017. Type 1 Diabetes Mellitus Impaired glucose utilization HYPERGLYCEMIA “CLASSIC TRIAD”: POLYURIA, POLYDIPSIA, POLYPHAGIA Severe cases: KETOACIDOSIS Fig 18.21 Kumar V. et al. Robbins Basic Pathology E-Book. Available from: VitalSource Bookshelf, (11th Edition). Elsevier Limited (UK), 2017 References/Resources Kumar V, et al. Robbins Basic Pathology E-Book. Available from: VitalSource Bookshelf, (11th Edition). Elsevier Limited (UK): pages 149-163 (autoimmune diseases), 645 (Graves disease), 655-665 (diabetes) Neville B, Damm D, Allen C, Chi A. Oral and Maxillofacial Pathology. Available from: VitalSource Bookshelf, (5th Edition). Elsevier Health Sciences (US): pages 307-309, 471-476, 798-806, 837-838, 844-846 Little JW, et al. Dental Management of the Medically Compromised Patient - E-Book. Available from: VitalSource Bookshelf, (10th Edition). Elsevier Health Sciences (US), 2023: pages 215-235 (diabetes), 249- 269 (thyroid disease), 310 -332(rheumatologic disorders).