Autoimmune and Inflammatory Disorders Flashcards
(109 cards)
1
Q
what is the definition of autoimmunity
A
presence of antibodies directed against normal host antigens
2
Q
what is the pathogenesis of SLE
A
- unknown etiology
- chronic, inflammatory autoimmune disorder
- vasculitis, fibrosis and tissue necrosis
3
Q
what are the complications of SLE
A
multi organ
4
Q
what is the epidemiology for SLE
A
- 90% of young middle aged women
- 2.5 times increased risk of AA
5
Q
what are the 11 criteria that need to be met for SLE dx
A
- arthritis
- serositis
- malar rash
- discoid rash
- photosensitivity
- oral ulcers
- renal disease
- neurological disease
- hematological disease
- immunological manifestations
- antinuclear antibodies
6
Q
what are the autoantibodies associated with SLE
A
- ANA: 95-100
- antinative DNA: 60
- RF: 20
- Anti-Sm: 10-25
- Anti-Ro: 15-20
- Anti-la: 5-20
7
Q
what is the management for SLE
A
- rheumatologists: organ specific approach
- long term prednisone
- immunomodulating agents
8
Q
what are the oral manifestations for SLE
A
- SLE like lichenoid lesions
- ulcerations/erosions
- hard palatal mucosa ulcer
- white radiating striae from a central ulcer
9
Q
what is the pathogenesis of sjogrens syndrome
A
- chronic, inflammatory, autoimmune disorder
- primary vs secondary SS
- unknwon etiology
- expression of MHC II moelcules 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 are elevated
10
Q
what are the complications of sjogrens syndrome
A
- lymphocytic infiltration
- lacrimal glands causing dry eyes (xerophthalmia)
-salivary glands causing dry mouth (xerostomia)
11
Q
what is the epidemiology for sjogrens syndrome
A
- eldery women
- female to male ratio is 9:1
12
Q
what is the dx for SS
A
- SS ACR classification criteria must have 2/3:
- positive anti-Ro and/or antiLa (+RF and ANA titer greater than 1:320)
- minor labial salivary gland biopsy exhibiting focal lymphocytic sialadenitis focus score greater than 1 focus
- ocular staining score greater than 3
13
Q
what is the management of SS
A
- rituximab
- long term prednisone
- immunomodulating agents
14
Q
what are the dental considerations for SS
A
- salivary hypofunction
- stimulated and unstimulated salivary flow measurements
- 44 times increased risk of MALToma
15
Q
what are the autoantibodies for SS
A
- ANA: 95
- Antinative DNA:0
- RF: 75
- anti-SM: 0
- anti- Ro: 60-70
- anti-La: 60-70
16
Q
what is the disease treated with azathioprine and SE
A
- RA
- stomatitis, nausea, vomiting, hepatotoxicity, pancytopenia, rash, arthralgia
17
Q
what is the disease treated with corticosteroids and SE
A
- RA, SLE
- candidiasis, HTN, osteoporosis, cataracts, peptic ulcers, psychosis, delayed wound healing
18
Q
what is the disease treated with cyclosporineand SE
A
- SLE, PSS
- stomatitis, cardiotoxicity, myelosuppresion, hepatotoxicity, pulmonary fibrosis, neoplasms, thrombocytopenia
19
Q
what is the disease treated with hydroxychloroquine and SE
A
- RA, SLE
- mucosal discoloration, lichenoid reactions, convulsions, retinal and corneal changes, leukopenia, thrombocytopenia, nausea, vomiting
20
Q
what is the disease treated with methotrexate and SE
A
-RA and SLE
- GI symptoms, stomatitis, rash, alopecia, infrequent myelosuppresion, hepatotozicity, rare pulmonary toxicity
21
Q
what is the disease treated with mycophenolate mofetil and SE
A
- RA, SLE
- hyper or hypotension, peripheral edema, chest pain, tachycardia, headache, insomnia, fever, dizziness, anxiety, rash, nausea, comiting, abdominal pain, diarrhea or consitpation, anorexia, dyspepsia, leukopenia, anemia, thrombocytopenia, leukocytosis, ascites, paresthesia, tremor, weakness, abnormal liver or kidney function, dyspnea, cough, sinusitis, pleural effusion. bacterial, candidal and herpetic infections
22
Q
what is the disease treated with NSAIDs and SE
A
- RA
- GI symptoms, including indigestion, ulceration, hemorrhage, small bowel ulceration, stomatitis, renal, neurological, pulmonary, hepatic, hematological, dermatological, displacement of protein bound drugs
23
Q
what are the immune mediated conditions
A
- contact stomatitis
- angioedema
- orofacial granulomatosis
- sarcoidosis
- erythema multiforme/stevens johnson syndrome/toxic epidermal necrolysis
- lichen planus
24
Q
what features are seen in melkerson rosenthal syndrome
A
- lip swelling
-fissured tongue - facial paralysis
25
what is the probability of chrons disease
over 22% of children diagnosed with OFG will have CD in 10 years and 8% are already dx
26
what sites are affects in chrons disease
- mostly swelling of lips
- 57% had swelling and 27% has cobblestoning on buccal mucosa
27
what is the gingival involvement with chrons disease
it ranges from segmental or diffuse erythema to edematous hyperplastic gingiva +/- pain
28
28% of patients with angular chelitis ____ had a staph aureus infection
61%
29
what are the characteristic of 35 OFG patients
- median age 24 years
- cobblestoning 49%
- fissuring 37%
- aphthous like ulceration 15%
- deeper linear type ulcers 12%
30
what are he percentages of food sensitivity
- benzoic acid (36%)
- food additives (33%)
- perfumes and flavourings (28%)
- cinnamaldehyde (27%)
- cinnamon (17%)
- benzoates (17%)
- chocolate (11%)
31
what is the treatment for food sensitivities
- topical/intralesional/systemic corticosteroids
- delayed release of triamcinolone
- various response
- adjuvant therapies: clofazimine, sulfasalazine, hydroxychloroquine, methotrexate, danazol, dapsone, TNF- alpha ant, metronidazole
32
what is sarcoidosis
- multisystem disease involves the lungs, eyes, and skin
- chest radiographic changes during a routine screening exam
- systemic symptoms: fatigue, night sweats, and weight loss
33
what is the pathogenesis of sarcoidosis
- development and accumulation of granulomas (compact, centrally organized collections of macrophages and eptiheliod cells encircled by lymphocytes)
- granulomas generally form to confine pathogens, restrict inflammation and protect surrounding tissue
- macrophages with chronic cytokine stimulation, differentiate into epitheliod cells, gain secretory and bactericidal capability, lose some phagocytic capacity and fuse to form multinucleated giant cells
34
describe lofgren's syndrom
- acute presentation
- arthritis, erythema nodosum, and bilateral hilar adenopathy
- erythema nodosum is observed predominantly in women
- marked ankle periarticular inflammation or arthritis without erythema nodosum is more common in men
35
what is the oral presentation of lofgren's syndrome
- plaque or nodular lesion
- tongue and lip
36
what is the dx for sarcoidosis
- chest radiographic evidence withc linical features and noncaseating granulomas on biopsy
- biopsy indicated for all patients with possible sarcoidosis except those with lofgrens syndrome
37
what are the clinical characteristics of sarcoidosis
- fatigue
- loss of ventricular function and sudden death
- cardiac and neurologic sarcoidosis
- chest radiographic patterns
38
what is the tx for sarcoidosis
- oral prednisone (20-40mg/day) international expert panel
- evaluate the response after 1-3 months
- if there has been a response the prednisone dose should be tapered to 5-15 mg per day with treatment planned for an additional 9-12 months
- lack of response after 3 months suggests the presence of irreversible fibrotic disease or an inadequate dose of prednisone
39
what is the transplantation with sarcoidosis
about 3% of lung transplantations and less than 1% of heart and liver transplantations are on pts with sarcoidosis
40
what is the prognosis for sarcoidosis
-2/3 of patients with sarcoidosis generally have a remission within a decade after dx
- a recurrence after 1 or more years of remission is uncommon
- less than 5% of pts die from sarcoidosis
- death as a result of pulmonary fibrosis with respiratory failure or of cardiac or neurologic involvement
41
describe erythema multiforme
- 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 classes exist
42
what is the epidemiology for erythema multiforme
- prevalence less than 1%
- young adults 20-40 years old
- 1:1.5 M:F ratio
- reported recurrence rate of 37%
-oral involvement as high as 70%
43
what is the clinical presentation for erythema multiforme
- vesiculobullous condition that may affect skin or mucous membranes
- symmetric involvement of extremities and trunk
- characteristic lesion: target lesion
- multiform clinical features: characteristic target lesions, macules, vesicles, papules
44
what is the clinical presentation of HAEM (herpes associated EM)
- no or mild prodromal symptoms
- more likely to be recurrent
45
what is the clinical presentation of DIEM (drug induced EM)
- flu like prodrome common
- less likely to be recurrent
46
what is the etiology and pathogenesis of HAEM
- 70-80% HSC infection is precipitating event
- HSV specific CD4+ Th1 cells and inflammatory cytokines recruit auto reactive CD8+ T cells
- CLA+ CD8+ 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
47
describe EM minor
- rashes/target lesions symmetrically distributed on extremities
- mucous membrane invovlement limited to one surface usually oral mucosa
48
describe EM major
- skin lesions may also be atypical -> raised, bullous
- involvement of multiple mucous membranes
49
what is classic EM
acute onset, self limiting, lasts 2-4 weeks
50
describe recurrent EM
more likely to be herpes associated
51
describe persistent EM
- rare
- continuous eruption of typical and atypical lesions
- often widespread and necrotic
- may be due to underlying viral infection, inflammatory condition, malignancy or idiopathic
52
what is the management of EM
- treatment of relevant infections or removal of causal drugs
- complete recovery usually in 2-4 weeks
- no treatment identified that predictably alters clincial course
- topical or systemic steroids: 0.5-1mg/kg/day tapered over 7-10 days
- steroid sparing agents
- lesions usually heal without scarring
53
describe Stevens Johnson syndrome
- severe cutaneous blistering hypersensitivity reaction clinically similar to EM but with more frequent mucosal involvement
- etiolgoy, genetic suscpetibility and pathomechanism distinct from EM
- etiology, genetic suscpetibility and pathomechanism identical to TEN
- now thought to form single disease entity, distinct from EM: SJS/TEN
54
what is stevens johnson/TEN caused by
drugs but infections may also play a role
55
what is the presentation of stevens johnson/TEN
- 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
56
what is the pathophysiology of stevens johnson/TEN
- 75% of SJS/TEN cases attributable to medications
- median latency time less than 4 weeks
- 74-94% of TEN cases attributable to medications or URT infection
- CD8+ T cells, mediated by cytokines likely play an important role in epidermal necrosis
- underlying mechanism still unknown
57
what is the prognosis of SJS/TEN
- prognosis depends on degree of epidermal invovlement
- SJS: 10%. mortality rate
- SJS/TEN overlap: 30% mortality rate
- TEN: up to 50% mortality rate:
- infection is most common cause of death
58
describe oral lichen planus and epidemiology
- T- cell immune mediated chronic mucocutaneous inflammatory disease
- stratified squamous epithelium of skin, oral mucosa, genital mucosa, larynx
- no circulating auto-antibodies
- unknown etiology
- 1-2% adult population
- age 30-60 years
- F >M 4:1
59
what is the most common skin condition with oral involvement
oral lichen planus
60
what are the predisposing factors for oral lichen planus
- lichenoid hypersensitivity reaction
- viral infections: HPV and Hep C
- DM
61
what causes lichenoid hypersensitvity reaction
- anti- HTN
- NSAIDs
- statins
- anti-DM agents
- amalgam restorations
- cinammon flavouring agents
- anti- hypothyroidism agents
62
what are the clinical features of lichen planus
- 10-15% have skin LP
- 6 P's: polygonal, pruritic, purple, papular, planar, plaques
- Koebner phenomenon
63
what is Koebner phenomenon
- Wickham striae on flexor surfaces of wrists
- LP lesions at sites of trauma
64
what are the clinical features of the reticular form of LP
- classic wickham striae
- bilateral BM
- attached gingiva
- ventral/dorsal tongue
65
what are the clincial features of erosive/ulcerative lichen planus
- most painful
- yellow fibrin membrane
- higher rate of malignant transformation
66
what is the histopath for lichen planus
- hyperkeratosis: orthokeratosis, parakeratosis
- chronic dense band like infilrate of lymphocytes
- saw tooth epithelial rete pegs/ridges
- degeneration of basal cell layer
- colloid/civette bodies: degenerating keratinocytes
67
what is the direct immunofluorescence for lichen planus
- shaggy/patchy/granular deposits of C3 fibrinogen at BMZ
68
what is the management for lichen planus
- cutaneous lesions: refer to dermatology
- topical: fluocinonide gel: 0.05% BID-QID and clobetasol gel 0.05% BID-QID
- kenalog 40mg (triamcinolone injection) 10 mg per 1cm ulcer
- dexamethasone 0.5mg/5ml BID-QID 5ml swish and spit 5mins
- clobetasol solution 0.05% BID-QID 5ml swish and spit 5mins
- tacrolimus 0.1% BID-QID 5ml swish and spit 5mins
- tacrolimus and clobetasol combined rinses
- systemic: prednisone 1mg/kg 5-7 days. plaquenil (hydroxychloroquine) 200mg BID
69
what is the mechanism of malignant potential in lichen planus
- chronic inflammation
- immune dysregulation
- topical/systemic immunosuppressants
-
70
what is the risk for malignant potential for lichen planus
- very low, 1/500-1000 OLP pts develop OSCC
- yet to be confirmed
- to date poorly documented
- erosive/ulcerative LP
- smokers and alcohol
- monitor LP anually
71
what are the vesiculobullous conditions
- pemphigus vulgaris
- bullous pemphigoid
- mucous membrane pemphigoid
- paraneoplastic pemphigus
72
what are the intraepithelial autoimmune bullous skin diseases
- pemphigus
- paraneoplastic pemphigus
73
what are the sub epithelial autoimmune bullous skin disease
-BP
- MMP
74
describe pemphigus vulgaris
- autoimmune vesiculobullous condition
- pemphigus subtypes
- incidence: 5/1,000,000 cases per year
- median age: 50 years
- no sex predilection
- mediterranean, south asian or jewish heritage
- HLA: DR4, DRw14 and DQB1 associated with PV
75
what are the pemphigus subtypes
- pemphigus vulgaris
- pemphigus vegetans
- pemphigus erythematosus
- pemphigus foliaceus
76
what are the clinical features of pemphigus vulgaris
- nikolsky sign
- asboe. hansen sign
77
what is the nikolsky sign
application of firm lateral pressure on normal appearng mucosa adjacent to a pre existing bulla induces new bulla formation
78
what is the asboe hansen sign
application of pressure directly to a bulla causes lateral extension
79
what are the oral features of pemphigus vulgaris
- first to show last to go
- oral lesions 1st sign greater than 50% of cases more than 1 year
- almost all have oral features
- most difficult to resolve with tx
- untreated oral and cutaneous lesions
- persist progressively involving more surfaces
80
what is the histology for pemphigus vulgaris
- intraepithelial separation
- acantholysis
- epithelial spinous layer cells fall apart
- rounded shape for loose cells (Tzanck cells)
- lamina propria
- mild-moderate chronic inflammatory cell infiltrate
81
what are the immunofluorescence studies for pemphigus
- DIF: intercellular IgG/IgM +/- C3
- InDIF & ELISA: positive in 8-90% of cases. circulating autoantibodies
82
what is the management for pemphigus vulgaris
- better prognosis if dx early
- prednisone
- alternate day prednisone and steroid sparing immunosuppressant
- steoid sparing agents
- monitor circulating autoantibody titres via inDIF to gauge success of tx
- 75% of patients have disease resolution in 10 years after tx
83
what are the steroid sparing agents
- azathioprine
- dapsone
- mycophenolate mofetil
- cyclophosamide
- IVIg
- plasmapheresis
- rituximab
84
what is the prevalence of bullous pemphigoid
- most common autoimmune blistering condition
- 1 in 100,000 anually
- age: 6-8th decade
- gender 2:1 male
- oral involvement is uncommon: 8-39%
85
what is the histopath for bullous pemphigoid
- perilesional biopsy
- subepithelial separation
- eosinophils within bulla
- acute and chronic inflammatory cells
86
what is the direct immunofluorescence of bullous pemphigoid
- BMZ: linear IgG and C3 (90-100%)
- hemidesmosomes: BP180, BP230
87
describe the indirect immunofluorescence with bullous pemphigoid
- antibody titers: 50-90% positive circulating autoantibodies. no correlation with disease activity
- binding of autoantibodies to BMZ
- starts the complement cascade
- degranulation of mast cells
- eosinophils and neutrophils recruitment
- elastases and matrix metalloproteinases
88
what is the management for bullous pemphigoid
- 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
- refractory cases: prednisone and cyclophosphamide
89
what are the alternative therapies for bullous pemphigoid
- dapsone
- tetracycline
- niacinamide
90
describe Mucous membrane pemphigoid and its prevalence
- chronic blistering mucocutaneous autoimmune disease
- autoantibodies to hemidesmosomes
- positive nikolsky sign
- unknown incidence: 2x as common as PV, most common oral AD
- age: 5-6th decade
- gender: 2:1 female
91
what are the subtypes of mucous membrane pemphigoid
- ocular involvement only
- oral invovlement only
- mucous and cutaneous involvement
- multiple mucosal sites without cutaneous involvement
- nose, esophagus, larynx, vagina
92
what are the ocular complications in MMP
- conjunctival mucosal scarring
- entropion
- symblepharon
- trichiasis
- scarring closes lacrimal gland openings: loss of tears, extremely dry, cornea produced excess keratin
- blindness if untreated, opacification from excess keratinization
93
what is the histopath for MMP
- perilesional biopsy
- BM separation
- subepithelial clefting
- inflammatory infiltrate superficial lamina propria
94
what is the direct immunofluorescence for MMP
- perilesional biopsy
- linear band IgG and C3 (90%)
- IgA and IgM (more severe)
95
describe indirect immunofluorescence in MMP
- MMP lacks detectable circulating autoantibody levels
- 5-25% pts are positive
- anti-epiligrin MMP
- autoantibodies to epiligrin
- more widespread invovlement
- oral MMP only
- autoantibodies to a6 integrin
96
what is the management for MMP
- referral to ophthalmologist: 25% of oral MMP pts develop ocular lesions
- referral to derm: 20% of MMP pts develop cutaneous lesions
- topical corticosteoids: 0.05% fluocinonide gel BID, 0.05% clobetasol gel BID
97
describe paraneoplastic pemphigus
- neoplasia induced pemphigus
- paraneoplastic autoimmune multi organ syndrome
- rare vesiculobullous disorder
- neoplasm history
98
what neoplasms are associated with PNP
- non hodgkin lymphoma (42%)
- chronic lymphocytic leukemia (29%)
- sarcoma (6%)
- thymoma (6%)
- castleman disease (6%)
99
what is the pathogenesis of PNP
- unknown
- multifaceted immunologic attack
- evidence suggest abnormal cytokine levels
- IL-6 produced by lymphocytes in response to tumor
- IL-6 stimulates abnormal production of antibodies
- antibodies against desmosomal complex antigens
- mediated by cytotoxic T lymphocytes in some cases
100
what are the clinical features of PNP
-PNP developed prior to malignancy dx: 1/3 of reported cases
- signs and symptoms: sudden appearance, poylmorphous
- cutaneous lesions: bullae -> erosions -> target lesions -> lichenoid lesions -> erythematous papules
- papular and pruritic
- palmar or plantar bullae
- vagina, respiratory tract, oral and conjunctival mucosa
101
what are the oral manifestations of PNP
- erythema multiforme like stomatitis
- hemorrhagic crusting of lip
- all sites
- oral involvement only in some cases
- mulitple painful irregular ulcers
102
what is the histopath for PNP
- non specific
- lichenoid mucositis
- intraepithelial clefting
- subepithelial clefting
103
describe direct immunofluorescence with PNP
- weakly positive linear IgG/C3 along intracellularly and BMZ
- InDIF: desmoplakin I and II, major bullous pemphigoid antigen, envoplakin, periplakin, desmoglein 1 and 3
104
what is the gold standard for PNP diagnosis
immunoblotting
105
what is immunoblotting with PNP
- characteristic reactivity with two plakin proteins is highly sensitive and specific for PNP
106
what is the management for PNP
- high morbidity and mortality (greater than 90%)
- complications from vesiculobullous lesions
- immunosuppressive therapy
- trigger a reactivation of malignant neoplasm
- 50% develop bronchiolitis obliterans
- systemic prednisone + immunosuppressant
- azathioprine
- methotrexate
- cyclophosphamide
107
what is the dx for major PNP
- polymorphic mucocutaneous eruption
- concurrent internal neoplasia
- serum antibodies with a specific immunoprecipitation pattern
108
what is the dx for minor PNP
- histologic evidence of acantholysis
- direct immunofluorescence showing intercellular and basement membrane staining
- indirect immunofluorescence staining with rate bladder epithelium
109
