Autoimmune & Inflammatory Disorders Flashcards
presence of antibodies (auto-antibodies or auto-reactive T-
cells) directed against normal host antigens (auto- or self-
antigens)
Autoimmunity
What are the autoantibodies seen in mucous membrane pemphigoid?
BP 180
BP 230
What are the autoantibodies seen in pemphigus vulgaris?
Demsoglein 1 and 3
Pathogenesis •Unknown etiology •Environmental triggers in a genetically predisposed individual •Chronic, inflammatory autoimmune disorder •Autoantibodies and immune complexes activate complement system •Vasculitis, fibrosis, tissue necrosis Complications Multi-organ Epidemiology •90% are young-middle aged women •2.5 times increased risk in AA
Systemic lupus erythematousus
What autoantibodies are present in SLE?
anti DS DNA and anti-SM
What other condition looks identical to SLE histologically and clinically intraorally?
Oral Lichen Planus
Which disease presents with a butterfly rash?
SLE
Management Rheumatologists: organ-specific approach •Long-term Prednisone •Immunomodulating agents (eg. mycophenolate mofetil, azathioprine, methotrexate) Oral Manifestations -lichenoid lesions •Ulcerations/erosions •Hard palatal mucosa ulcer •White radiating striae from a central ulcer
SLE
The following are dental considerations needing to be taken if pt has \_\_\_\_\_\_: Determine the status of the stability of their disease Leukopenia •Immunosuppressive rx Thrombocytopenia (25% of pts) •extreme thrombocytopenia (<20,000 platelets) Nonbacterial verrucous valvular Libman– Sacks endocarditis •most common cardiac lesion Renal disease •localization of immune complexes in the kidney is the precipitating factor in the development of lupus nephritis •rapidly progressing glomerulonephritis or a less aggressive form Neuropsychiatric disease •psychosis, seizures, cerebrovascular accidents
SLE
Pathogenesis •Unknown etiology •Environmental, hormonal, infectious factors, in a genetically predisposed individual •external trigger (infection, trauma) elicits an autoimmune reaction •hypertrophy of the synovial lining of the joint and endothelial cell activation •uncontrolled inflammation and destruction of cartilage and bone
Rheumatoid arthritis
•1.3 million US adults •Women 3 times more affected than men •sex difference diminish in older age groups, suggesting a hormonal component Diagnosis 6/10 score based on a 4-prong algorithm: 1. joint involvement 2. serology test results (Rheumatoid factor, ACPA anticitrullinated protein antibody) 3. acute-phase reactant test results (CRP, ESR) 4. pt self-reporting of signs/symptom duration
Rheumatoid arthritis
What lab value will be higher in Rheumatoid arthritis?
Rheumatoid factor
Management Nonpharmacological •Physical, occupational therapies, orthotic devices, surgery Pharmacological •NSAIDs, disease-modifying antirheumatic drugs, immunosuppressants, biological response modifiers, corticosteroids Oral Manifestations •TMJ dysfunction •Medication induced ulcerations •Salivary hypofunction Dental Considerations See ADA guideline on prophylactic antibiotics for pts with prosthetic joints undergoing dental procedures
Rheumatiod arthritis
Pathogenesis •Unknown etiology •Endothelial cell injury •Fibroblast activation •Vascular dysfunction Complications •skin thickening/induration •tissue fibrosis and chronic inflammation •infiltration of heart, lungs and kidneys •prominent fibroproliferative vascular disease Epidemiology •Peak onset (30–50 years) •4-9 times higher in women than in men
Progressive Systemic Sclerosis
Scleroderma
Diagnosis Localized scleroderma: •skin on the hands and face •slow disease course •indolent and rarely spreads more widely or results in serious complications Systemic scleroderma: •affects large areas of skin and heart, lungs, or kidneys 2 main types of systemic scleroderma: (1) limited disease or CREST syndrome, calcinosis, Raynaud’s syndrome, esophageal dysmotility, sclerodactyly, telangiectasia (2) diffuse disease
Systemic sclerosis
Management •Long-term Prednisone
•Immunomodulating agents (eg.
mycophenolate mofetil, azathioprine,
methotrexate)
Oral Manifestations Severe microstomia, trismus, submucosal
fibrosis
Dental Considerations Elongation exercises to improve trismus
Systemic sclerosis
Pathogenesis •Chronic, autoimmune, inflammatory disorder •Primary vs Secondary SS (RA, SLE) •Unknown etiology •expression of MHC-II molecules in activated salivary gland cells •inherited susceptibility markers trigger a chronic inflammatory response in genetically susceptible individuals •ongoing activation of the innate immune system as pro- inflammatory cytokines (eg. IFN-g) are elevated Complications •Lymphocytic infiltration •lacrimal glands causing dry eyes (xerophthalmia) •salivary glands causing drymouth (xerostomia)
Sjogren’s syndrome
Epidemiology •Elderly women •Female-to-male ratio is 9 : 1 Diagnosis SS ACR Classification Crietria (2/3) 1. Positive anti-Ro and/or anti-La or (+RF and ANA titer >1:320) 2. Minor labial salivary gland biopsy exhibiting focal lymphocytic sialadenitis focus score >1 focus/4mm2 3. Ocular staining score >3 Management •Rituximab (anti-CD20 monoclonal antibodies) •Long-term Prednisone •Immunomodulating agents (eg. mycophenolate mofetil, azathioprine, methotrexate) Dental Considerations Salivary hypofunction •stimulated and unstimulated salivary flow measurements •44 times increased risk of MALToma
Sjogren’s Syndrome
Deficiency of C1 esterase inhibitor so can’t inhibit bradykinin which results in increase vasodilation and vascular permeability
hereditary angioedema
\_\_\_\_\_ is idiopathic or immune mediated - angular chelitis -Lip swelling -Tongue fissuring -Cobblestoning -Uclers Ranges from segmental or diffuse erythema to edematous hyperplastic gingiva +/- pain Stag horn appearance -Median age 24 -Food sensitivity can trigger this Tx: -Diet modification •Topical/intralesional/systemic corticosteroids •delayed release triamcinolone •Various response •Adjuvant therapies •clofazimine, sulfasalazine, hydroxychloroquine, methotrexate, danazol, dapsone, TNF-alpha ant., metronidazole
Orofacial granulomatosis
The following 3 signs signal what syndrome?
•Lip swelling
•Fissured tongue
•Facial paralysis
Melkerson-Rosenthal Syndrome
What other systemic disease is more likely to be present with orofacial granulomatosis
Chron’s disease
What variable is seen most frequently in a OFG pt that has Chron’s?
Ulcers
What other bacterial species can cause angular chelitis besides candida?
S. Aureus
•Multisystem diseases involves the lungs, eyes, and skin •Chest radiographic changes during a routine screening examination •Systemic symptoms: fatigue, night sweats, and weight loss Oral Presentation •Plaque or nodular lesion •Tongue and lip Treatment •Oral prednisone (20 to 40 mg/day); international expert panel •Evaluate the response after 1 to 3 months •If there has been a response, the prednisone dose should be tapered to 5 to 15 mg per day, with treatment planned for an additional 9 to 12 months •Lack of a response after 3 months suggests the presence of irreversible fibrotic disease, or an inadequate dose of prednisone
Sarcoidosis
Pathogenesis of _____
•Development and accumulation of granulomas (Compact,
centrally organized collections of macrophages and
epithelioid cells encircled by lymphocytes)
•Granulomas generally form to confine pathogens, restrict
inflammation, and protect surrounding tissue
•Macrophages, with chronic cytokine stimulation,
differentiate into epithelioid cells, gain secretory and
bactericidal capability, lose some phagocytic capacity, and
fuse to form multinucleated giant cells
Sarcoidosis
•Acute presentation •Arthritis, erythema nodosum, and bilateral hilar adenopathy (9 to 34% of patients) •Erythema nodosum is observed predominantly in women •Marked ankle periarticular inflammation or arthritis without erythema nodosum is more common in men
-seen in sarcoidosis
Lofgren’s syndrome
•Acute hypersensitivity reaction to various antigens
•Characterized clinically by target lesions distributed symmetrically
on extremities and trunk
•Usually self-limiting but may be recurrent
•Many different classifications exist
Epidemiology
•Prevalence < 1%
•Young adults 20-40 years old
•1:1.5 M:F ratio
•Reported recurrence rate: 37%
•Oral involvement: as high as 70%
Erythema multiforme
Clinical presentation
•Vesiculobullous condition that may affect skin or mucous
membranes
•Symmetric involvement of extremities and trunk
•Characteristic lesion: target/iris lesion
•‘Multiform’ clinical features:
•Characteristic target lesions
•Macules
•Vesicles
•Papules
Management
•Treatment of relevant infections or removal of causal drugs
•Complete recovery usually occurs in 2-4 weeks
•No treatment identified that predictably alters clinical course
•Topical or systemic steroids
•0.5-1.0 mg/kg/day tapered over 7-10days
•Steroid sparing agents
•Lesions usually heal without scarring
Erythema multiforme
What viruses are most commonly associated with Erythema multiforme?
HSV 1 and 2
What bacteria is most common in erythema multiforme?
Mycoplasma pneumoniae
____ associated EM
•No or mild prodromal symptoms
•More likely to be recurrent
•70-80%: HSV infection is precipitating event
•HSV-specific CD4+ Th1 cells and inflammatory cytokines (IFN-γ)
recruit auto-reactive CD8+ T-cells
•CLA+ (skin-homing) CD8+ T-cells triggered by viral antigen-positive
cells
•Keratinocyte growth arrest
•Keratinocyte lysis and apoptosis
•Release of cytotoxic factors
•Mechanism of auto-reactive T-cell generation unclear
HAEM (Herpes associated EM):
_____ induced EM):
•Flu-like prodrome common
•Less likely to be recurrent
DIEM (drug induced
•EM ____:
•Rashes/target lesions symmetrically distributed on extremities
•Mucous membrane involvement limited to one surface ->
typically oral mucosa
minor:
EM _____:
•Skin lesions may also be atypical -> raised, bullous
•Involvement of multiple mucous membranes
major:
•Severe cutaneous blistering hypersensitivity reaction clinically
similar to EM but with more frequent mucosal involvement
•Etiology, genetic susceptibility, and pathomechanism distinct from
EM
•Etiology, genetic susceptibility, and pathomechanism identical to
Toxic epidermal necrolysis
•Now thought to form single disease entity, distinct from EM:
SJS/TEN
Stevens-Johnson syndrome
•Severe cutaneous adverse reaction that affects skin and
mucosal surfaces
•Erythema and blister formation of varying extent
•Hemorrhagic erosions of mucous membranes
•Fever and malaise:
•Often first sign of disease
•May persist after mucocutaneous lesions appear
•Mainly caused by drugs but infections and other unidentified
risk factors may play a role
SJS/Toxic
epidermal necrolysis
•T-cell immune mediated chronic muco-cutaneous inflammatory disease •Stratified squamous epithelium of skin, oral mucosa, genital mucosa, larynx •Is it an auto-immune condition? •No circulating auto-antibodies •Unknown etiology •1-2% adult population •Most common skin condition with oral involvement •Age: 30-60yrs •F>M (1.4:1) Clinical Features •10-15% have skin LP •6 P’s •Polygonal •Pruritic •Purple •Papular •Planar •Plaques •Koebner phenomenon •Wickham striae on flexor surface of wrists •LP lesions at sites of trauma
Oral lichen planus
Histopath of \_\_\_\_\_\_ •Chronic dense band-like infiltrate of lymphocytes •Saw tooth epithelial rete pegs/ridges •Degeneration of basal cell layer •Colloid/Civette bodies •degenerating keratinocytes
Oral lichen planus
•Autoimmune vesicullobullous condition
Many subtypes
•Incidence: 5/1,000,000 cases per year
•Median Age: 50 yrs
•No sex predilection
•Mediterranean, South Asian or Jewish heritage
•HLA-DR4, DRw14 & DQB1 associated with PV
PV
•application of firm lateral pressure on normal-appearing mucosa adjacent to a pre-existing bulla induces new bulla formation
Nikolsky sign
•application of pressure
directly to a bulla causes
lateral extension
Asboe-Hansen sign
Oral Features •“first to show, last to go” •oral lesions 1st sign >50% of cases >1 year •almost all have oral features •most difficult to resolve with tx •Untreated oral & cutaneous lesions •persist progressively involving more surfaces Histopath: •Intraepithelial separation •Acantholysis •epithelial spinous layer cells fall apart •rounded shape for loose cells (Tzanck cells) •Lamina propria •mild-moderate chronic inflammatory cell infiltrate
Pemphigus vulgaris
What are the 3 conditions that Tzank cells can be seen in?
EM
PV
HSV
What is the tx that must be used for pt with PV?
Long term corticosteroids
•Most common autoimmune blistering condition •1 in 100,000 annually •Age: 6th-8th decade •Gender: 2:1 male •Oral involvement is uncommon •8-39% - Skin only •Good prognosis •spontaneous remission after 2-5 years •up to 27% mortality rate •Systemic immunosuppressive therapy •Prednisone QD/QOD •Azathioprine added if no response •Alternative therapies •Dapsone •Tetracycline •Niacinamide •Refractory cases •Prednisone & Cyclophosphamide
Bullous pemphigoid
- Chronic, blistering, mucocutaneous autoimmune disease
- Autoantibodies to hemidesmosomes
- Positive Nikolsky sign
- Unknown incidence
- 2x as common as PV
- most common oral AD
- Age: 5th-6th decade
- Gender: 2:1 female
- Ocular involvement only
- Oral involvement only
- Mucosal & cutaneous involvement
- Multiple mucosal sites without cutaneous involvement
- nose, esophagus, larynx, vagina
Mucous Membrane Pemphigoid (MMP)
•Conjunctival mucosal scarring •Entropion •Symblepahron •Trichiasis •Scarring closes lacrimal gland openings •loss of tears •extremely dry •cornea produces excess keratin •Blindness •if untreated •opacification from excess keratinization •Referral to an ophthalmologist •25% of oral MMP pts develop ocular lesions •Referral to a dermatologist •20% of oral MMP pts develop cutaneous lesions •Topical corticosteroids (custom trays) •0.05% fluocinonide gel BID •0.05% clobetasol gel BID
MMP
- Neoplasia-induced Pemphigus
- Paraneoplastic Autoimmune Multi-organ Syndrome (PAMS)
- Rare vesicullobullous disorder
- 150 documented cases
- Neoplasm hx
- Non-Hodgkin Lymphoma (42%)
- Chronic Lymphocytic Leukemia (29%)
- Sarcoma (6%)
- Thymoma (6%)
- Castleman Disease (6%)
Pathogenesis
•Unknown
•Multifaceted immunologic attack
•Evidence suggests abnormal cytokine levels
•IL-6 produced by lymphocytes in response to patient’s tumor
•IL-6 stimulates abnormal production of antibodies
•antibodies against desmosomal complex antigens
•Mediated by cytotoxic T-lymphocytes in some cases
Paraneoplastic Pemphigus
PNP
What 2 conditions are seen with PNP?
Non hodgkin lymphoma
Oral Manifestations “Erythema multiforme- like stomatitis” •Hemorrhagic lip crusting •All sites •Oral involvement only in some cases •Multiple painful irregular ulcers Management •High morbidity & mortality (>90%) •complications from vesiculobullous lesions •immunosuppressive therapy •trigger a reactivation of malignant neoplasm •~ 50% develop bronchiolitis obliterans •Systemic prednisone + immunosuppressant •azathioprine •methotrexate •cyclophosphamide
Paraneoplastic pemhigus
What autoantibodies are seen in PNP?
Plakins
