Immunologic Diseases II Flashcards
(159 cards)
1
Q
What are the autoimmune and connective tissue diseases?
A
- Systemic Lupus Erythematosus
- Rheumatoid Arthritis
- Progressive Systemic Sclerosis
- Sjögren’s Syndrome
2
Q
What are the immune-mediated conditions?
A
- Contact Stomatitis
- Angioedema
- Orofacial Granulomatosis
- Sarcoidosis
- Erythema Multiforme/Stevens–Johnson Syndrome/Toxic Epidermal Necrolysis
- Lichen Planus
3
Q
What are the vesiculobullous conditions?
A
- Pemphigus Vulgaris
- Bullous Pemphigoid
- Mucous Membrane Pemphigoid
- Paraneoplastic Pemphigus
4
Q
What is the definition of autoimmunity?
A
presence of antibodies (auto-antibodies or auto-reactive Tcells) directed against normal host antigens (auto- or self-antigens)
5
Q
What is the pathogenesis of systemic lupus erythematosus?
A
- Unknown etiology
— Environmental triggers in a genetically predisposed individual - Chronic, inflammatory autoimmune disorder
— Autoantibodies and immune complexes activate complement system
— Vasculitis, fibrosis, tissue necrosis
6
Q
What type of complications are associated with systemic lupus erythematosus?
A
Multi-organ
7
Q
What is the epidemiology of systemic lupus erythematosus?
A
- 90% are young-middle aged women
- 2.5 times increased risk in AA
8
Q
How can you diagnose systemic lupus erythematosus?
A
Diagnosis of SLE requires 4 of the 11 criteria to be met:
- Arthritis
- Serositis (pleuritis or pericarditis)
- Malar rash (butterfly rash)
- Discoid rash
- Photosensitivity
- Oral ulcers
- Renal disease
- Neurological disease (psychosis or seizures)
- Hematological disease (hemolytic anemia, thrombocytopenia, leukopenia, or lymphopenia)
- Immunological manifestations (anti-DS DNA, anti-SM, antiphospholipid antibodies)
- Antinuclear antibodies
9
Q
A
malar rash
- SLE
10
Q
What is the first screening autoantibody that is tested?
A
ANA
11
Q
What are the types of autoantibodies tested for SLE, RA, SS, and diffuse scleroderma?
A
- ANA
- antinative DNA
- RF
- anti-Sm
- anti-Ro
- anti-La
12
Q
What are the autoantibody panels for different types of autoimmune diseases (image)?
A
13
Q
What is the management of systemic lupus erythematosus?
A
Rheumatologists: organ-specific approach
* Long-term Prednisone
* Immunomodulating agents (eg. mycophenolate mofetil, azathioprine, methotrexate)
14
Q
What are the oral manifestations of systemic lupus erythematosus?
A
SLE-like lichenoid lesions
* Ulcerations/erosions
* Hard palatal mucosa ulcer
* White radiating striae from a central ulcer
15
Q
What are the dental considerations for systemic lupus erythematosus?
A
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
16
Q
What is the pathogenesis of rheumatoid arthritis?
A
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
17
Q
What is the main complication with rheumatoid arthritis?
A
Joints and extra-articular involvement
18
Q
A
hypertrophy of the synovial lining of the joint
- Rheumatoid arthritis
19
Q
What is the epidemiology of rheumatoid arthritis?
A
- 1.3 million US adults
- Women 3 times more affected than men
— sex difference diminish in older age groups, suggesting a hormonal component
20
Q
How do you diagnose rheumatoid arthritis?
A
6/10 score based on a 4-prong algorithm:
- 1. joint involvement
- 2. serology test results (Rheumatoid factor, ACPA anticitrullinatedprotein antibody)
- 3. acute-phase reactant test results (CRP, ESR)
- 4. ptself-reporting of signs/symptom duration
21
Q
What autoantibody is usually high in those with rheumatoid arthritis?
A
RF
22
Q
What are the clinical features of rheumatoid arthritis?
A
- multiple symmetric joint involvement
- significant joint inflammation
- morning join stiffness lasting longer than 1 hour
- symmetric, spindle-shaped swelling of PIP joints and volar subluxaion of MCP joints and Bouchard’s nodes of PIP
- systemic manifestations (fatigue, weakness, malaise)
23
Q
What are the clinical features of osteoarthritis?
A
- usually one or two joints involved
- joint pain usually without inflammation
- morning joint stiffness lasting less than 15 minutes
- Heberden nodes of DIP joints
24
Q
What is the management of rheumatoid arthritis?
A
- Nonpharmacological
— Physical, occupational therapies, orthotic devices, surgery - Pharmacological
— NSAIDs, disease-modifying antirheumaticdrugs, immunosuppressants, biological response modifiers, corticosteroids
25
What are the oral manifestations of rheumatoid arthritis?
* TMJ dysfunction
* Medication induced ulcerations
* Salivary hypofunction
26
What are the dental considerations of rhematoid arthritis?
See ADA guideline on prophylactic antibiotics for ptswith prosthetic joints undergoing dental procedures
27
What rheumatoid arthritis complication is shown here?
anterior open bite resulting from progressive bilateral condylar resorption in a patient with advanced RA
28
What rheumatoid arthritis complication is shown here?
lateral skull film shows a swan-neck deformity (complications with dental chair position)
29
In general, for patients with prosthetic joint implants, prophylactic antibiotics _______ recommended prior to dental procedures to prevent prosthetic joint infection
are not
30
What are the possible harms of antibiotics?
anaphylaxis, antibiotic resistance, and opportunistic infections like C diff
31
What is the suggested antibiotic prophylaxis regimen for patients no allergic to penicillin?
Cephalexin, Cefradine, Amoxicillin
- 2g orally 30 min - 1 hour before dental procedure
32
What is the suggested antibiotic prophylaxis regimen for patients no allergic to penicillin and are unable to take oral medications?
Cefazolin, Ampicillin
- Cefazolin 1g or ampicillin 2g intramuscularly or intravenously 30 min-1 hr before dental procedure
33
What is the suggested antibiotic prophylaxis regimen for patients allergic to penicillin?
Clindamycin
- 600 mg orally 30 min - 1 hr before dental procedure
| clindamycin can cause bad tummy problems :(
34
What is the suggested antibiotic prophylaxis regimen for patients allergic to penicillin and unable to take oral medications?
Clindamycin
- 600 mg intravenously 30 min - 1 hr before dental treatment
| clindamycin can cause bad tummy problems :(
35
What is the pathogenesis of progressive systemic sclerosis (scleroderma)?
Unknown etiology
* Endothelial cell injury
* Fibroblast activation
* Vascular dysfunction
36
What are the complications with progressive systemic sclerosis (scleroderma)?
* skin thickening/induration
--- tissue fibrosis and chronic inflammation
--- infiltration of heart, lungs and kidneys
* prominent fibroproliferativevascular disease
37
What is the epidemiology of progressive systemic sclerosis (scleroderma)?
* Peak onset (30–50 years)
* 4-9 times higher in women than in men
38
What complication associated with progressive systemic sclerosis (scleroderma) is shown?
sclerodactyly
- think, taut, scared, fibrous skin
39
What complication associated with progressive systemic sclerosis (scleroderma) is shown?
Raynaud's syndrome (purple tone to fingertips of cyanotic phase)
40
How do you diagnose localized progressive systemic sclerosis (scleroderma)?
Localized scleroderma:
* skin on the hands and face
* slow disease course
* indolent and rarely spreads more widely or results in serious complications
41
How do you diagnose systemic progressive systemic sclerosis (scleroderma)?
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
42
What are the positive autoantibodies in diffuse scleroderma?
ANA
RF
43
What is the management of progressive systemic sclerosis (scleroderma)?
* Long-term Prednisone
* Immunomodulating agents (eg. mycophenolate mofetil, azathioprine, methotrexate)
44
What are the oral manifestations of progressive systemic sclerosis (scleroderma)?
- Severe microstomia (shown in image)
- trismus
- submucosal fibrosis
45
What are the dental considerations of progressive systemic sclerosis (scleroderma)?
Elongation exercises to improve trismus
46
What is the pathogenesis of sjogrens syndrome?
* Chronic, autoimmune, inflammatory disorder
* Primary vsSecondary 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 proinflammatory cytokines (eg. IFN-g) are elevated
47
What are the complications associated with sjogrens syndrome?
Lymphocytic infiltration
* lacrimal glands causing dry eyes (xerophthalmia)
* salivary glands causing dry mouth (xerostomia)
48
What are the clinical complications of xerostomia associated with sjogrens syndrome?
- a) dry, pebbly appearance of tongue
- b) dry, slick tongue and angular cheilitis
- c) rampant dental caries
- d) cuspal dental caries
49
What is the epidemiology of sjogrens syndrome?
* Elderly women
* Female-to-male ratio is 9 : 1
50
How do you diagnose sjogrens syndrome?
SS ACR Classification Crietria(2/3)
- 1. Positive anti-Ro and/oranti-La or (+RF and ANA titer >1:320)
- 2. Minor labial salivary gland biopsy exhibiting focal lymphocytic sialadenitisfocus score >1 focus/4mm2
- 3. Ocular staining score >3
51
What is the management of sjogrens syndrome?
* Rituximab (anti-CD20 monoclonal antibodies)
* Long-term Prednisone
* Immunomodulatingagents (eg. mycophenolatemofetil, azathioprine, methotrexate)
52
What are the dental considerations for sjogrens syndrome?
Salivary hypofunction
- stimulated and unstimulated salivary flow measurements
44 times increased risk of MALToma (increased risk of lymphoma)
53
What are the autoantibodies associated with sjogrens syndrome?
- ANA
- RF
- anti-Ro
- anti-La
54
What is the treatment for moisture and lubrication for sjogrens syndrome?
- drink water and liquids
- use sugarless candy or gum
- avoid ethanol, tobacco, coffee, tea, caffeinated beverages
- oasis, salivart, **biotene**
- **pilocarpinine** hydrochloride
- **cevimeline** hydrocholoride
- sodium carboxymethylcellulose
55
What is the treatment for soft tissue lesions and soreness for sjogrens syndrome?
- oasis, salivart
- benadryl + maalox + nystatin elixir
- decadron
- triamcinolone
- orbase-HCA
- mycelex
- Mycolog II ointment
56
What are the prevention methods against caries and periodontal disease for sjogrens syndrome?
- meticulous perioral hygiene
- avoid acids
- regular hygiene recalls
- sodium bicarb rinses
- biotene toothpaste
- **prevident**
- **peridex**
- waterpik
57
What are the guidelines for treatment patients with connective tissue diseases before dental care?
- **med consult**
- obtain baseline CBC
- consider routine chemicstry panel (lupus)
- **postpone elective care** (with flare ups)
- prescribe prophylactic antibiotics if indicated
- use strss-reducing measures
- **be prepared for medical emergencies**
58
What are the guidelines for treatment patients with connective tissue diseases during dental care?
- assess oral mucosal disease and TMJ involvement
- assess xerostomia
- assess facial muscular pain and dysfunction
- use sutures and adjunciv ehemostatic agents
- use stress-reducing measures
59
What are the guidelines for treatment patients with connective tissue diseases after dental care?
- use appropriate dosing intervals of meds
- use caution with NSAIDs/asprin (RA)
- consider oral suspension meds (scleroderma)
- evaluate TMJ dysfunction
- schedule frequent recall maintence
60
What is azathioprine used to treat and why is it potential toxic?
RA
61
What is corticosteroids used to treat and why is it potential toxic?
RA, SLE
62
What is cyclophosphamide used to treat and why is it potential toxic?
SLE, PSS
63
What is hydroxychloroquine sulfate used to treat and why is it potential toxic?
RA, SLE
64
What is methotrexate used to treat and why is it potential toxic?
RA, SLE
65
What is mycophenolate mofetil used to treat and why is it potential toxic?
RA, SLE
66
What is NSAIDs used to treat and why is it potential toxic?
RA
67
What are the considerations for the patient evaluation and risk assessment?
| ABCDEF
**A**nalgsics
**A**ntibiotics
**A**nesthesia
**A**llergy
**B**leeding
**B**lood pressure
**C**hair position
**D**evices
**D**rugs
**E**quipment
**E**mergencies
**F**ollow-up
68
What is a type I reaction?
IgE-mediated hypersensitivity
69
What is a type II reaction?
IgG-mediated cytotoxic hypersensitivity
70
What is a type III reaction?
immune complex-mediated hypersensitivity
| most autoimmune diseases
71
What is a type IV reaction?
cell-mediated hypersensitivity
72
angioedema
| acute
73
What are the two hypotheses for angioedema?
- hereditary angioedema
--- deficiency of C1 esterase inhibitor
- allergic response angioedema
74
orofacial granulomatosis (OFG)
| idiopathic, immune mediated, chronic
75
What is melkerson-rosenthal syndrome?
* Lip swelling
* Fissured tongue
* Facial paralysis
76
Do patients with orofacial granulomatosis need a colonoscopy?
YES
77
What is the probability of developing crones disease if you have orofacial granulomatosis?
Over 22% of children dx with OFG will have CD in 10 years and 8% are already dx
78
What sites are most affected by orofacial granulomatosis (OFG)?
* Mostly swelling of lips
* 57% had swelling and 27% had cobblestoning on BM
79
Is there gingival involvment with orofacial granulomatosis (OFG)?
yes
- Ranges from segmental or diffuse erythema to edematous hyperplastic gingiva +/- pain
80
What is this finding called associated with OFG and crohns?
stag-horn appearance on the floor of mouth
81
What is the percentage of patients that have OFG who have angular cheilitis?
28% of which 61% had Staph. aureus infection
82
What are the characteristics of OFG patients?
* Median age 24 years
* Cobblestoning 49%
* Fissuring 37%
* Aphthous-like ulceration 15%
* Deeper linear-type ulcers 12%
83
What types of foods cause sensitivity with OFG?
* Benzoic acid (36%)
* Food additives (33%)
* Perfumes and flavourings (28%)
* Cinnamaldehyde (27%)
* Cinnamon (17%)
* Benzoates (17%)
* Chocolate (11%)
84
What is the pathology of OFG?
- true granuloma
- multinucleated giant cells and lymphocytes
- collection of epithelial histocytes
85
What is the treatment for OFG?
* Topical/intralesional/systemic corticosteroids
--- delayed release triamcinolone
* Various response
* Adjuvant therapies
--- clofazimine, sulfasalazine, hydroxychloroquine, methotrexate, danazol, dapsone, TNF-alpha ant., metronidazole
86
What is sarcoidosis?
| not autoimmune
* Multisystem diseases involves the lungs, eyes, and skin
* Chest radiographic changes during a routine screening examination
* Systemic symptoms: fatigue, night sweats, and weight loss
87
What is the pathogenesis of sarcoidosis?
* 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
88
What is Lofgren's syndrome?
* Acute presentation of **sarcoidosis**
* 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
89
What does the histology of sarcoidosis look like?
- macrophages surrounded by a rim of leukocytes
- not a true granuloma
89
What is the oral presentation of sarcoidosis?
* Plaque or nodular lesion
* Tongue and lip
90
How do you diagnose sarcoidosis?
- chest radiographic evidence
- noncaseating granulomas on biopsy
- serum angiotensin-coverting enzyme level (not super diagnostic)
- PET
91
What are the clinical characteristics of sarcoidosis?
- constitutional syptoms (fatigue
- cardiac sarcoidosis
--- loss of ventricular function and sudden death
- cardiac and neurologic sarcoidosis
92
What is the treatment for sarcoidosis?
* 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
93
What are the facts about transplanation in patients with sarcoidosis?
About 3% of lung transplantations and less than 1% of heart and liver transplantations are performed in patients with sarcoidosis
94
What is the prognosis of sarcoidosis?
* 2/3 of patients with sarcoidosis generally have a remission within a decade after diagnosis
* A recurrence after 1 or more years of remission is uncommon (affecting <5% of patients)
* Less than 5% of patients die from sarcoidosis
* Death as a result of pulmonary fibrosis with respiratory failure or of cardiac or neurologic involvement
95
What is 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 classifications exist
96
What is the epidemiology for erythema multiforme?
* Prevalence < 1%
* **Young adults** 20-40 years old
* 1:1.5 M:F ratio
* Reported recurrence rate: 37%
* Oral involvement: as high as 70%
97
What is the clinical presentation of erythema multiforme?
* 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
--- Papule
98
What is this complication called which is associated with erythema multiforme?
target lesions
99
Approximately ___% of cases of erythema multiforme are viral (some bacterial) in origin
90%
## Footnote
viral - Herpes
bacterial - mycoplasma pneumoniae
100
Approximately ___% of cases of erythema multiforme are drug related
10%
## Footnote
sulfonamides
NSAIDs
101
What is the clinical presentation of erythema multiforme?
HAEM (Herpes associated EM):
* No or mild prodromal symptoms
* More likely to be recurrent
DIEM (drug induced EM):
* Flu-like prodrome common
* Less likely to be recurrent
102
What is the etiology/pathogenesis of HAEM?
| herpes associated erythema multiforme
* 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
103
What does the histology of erythema multiforme look like?
- necrosis of epithelium
- cells balloon and splitting
104
erythema multiforme
105
What is erythema multiforme minor?
* Rashes/target lesions symmetrically distributed on extremities
* Mucous membrane involvement limited to one surface -> typically oral mucosa
106
What is erythema multiforme major?
* Skin lesions may also be atypical -> raised, bullous
* Involvement of multiple mucous membranes
107
What is classic erythema multiforme?
* Acute onset, self-limiting, lasts 2-4 weeks
108
What is recurrent erythema multiforme?
* More likely to be Herpes-associated
109
What is persistent erythema multiforme?
* Continuous eruption of typical and atypical lesions
--- Often widespread and necrotic
* May be due to underlying viral infection, inflammatory condition, malignancy, or idiopathic
110
What is the management of erythema multiforme?
* 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
111
What is Stevens-Johnson syndrome?
* 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
112
What is toxic epidermal necrolysis/SJS?
* 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
* Mainly caused by drugs but infections and other unidentified risk factors may play a role
113
steven-johnson syndrome
| DD: pemphigus vulgaris
114
toxic epidermal necrolysis
115
SJS/TEN
| severe lip crusting (hemmoragic crusting) = SJS/TEN
116
What is the pathophysiology of SJS/TEN?
* 75% of SJS/TEN cases attributable to medications
--- Median latency time: < 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
117
What is the prognosis for SJS/TEN?
* Prognosis depends on degree of epidermal involvement
--- SJS: 10% mortality rate
--- SJS/TEN overlap: 30% mortality rate
--- TEN: up to 50% mortality rate
* Infection is most common cause of death
118
What is oral lichen planus (OLP)?
* 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)
119
What are the predisposing factors for oral lichen planus (OLP)?
* Lichenoid hypersensitivity reaction
--- Clinically & histologically indistinguishable from LP
--- medications
* Viral infections
* Diabetes Mellitus
120
What are the clinical features of oral lichen planus?
* 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
--- Does Koebnerization occur in the oral cavity? IT CAN!
121
What is the reticular form of lichen planus?
* Classic wickham striae
* Bilateral BM
* Attached gingiva
* Ventral/dorsal tongue
122
What is the erosive form of lichen planus?
* Most painful
* Yellow fibrin membrane
* Higher rate of malignant transformation
123
What is the histology of lichen planus?
* Hyperkeratosis
* Chronic **dense bandlike infiltrate** of lymphocytes
* **Saw tooth** epithelial rete pegs/ridges
* Degeneration of basal cell layer
* Colloid/Civette bodies
124
What does direct immunofluorescence show about lichen planus?
* Shaggy/patchy/granular deposits of C3 fibrinogen at BMZ
125
What is the management of lichen planus?
* Cutaneous lesions - Refer to dermatology
* Topical meds
* Systemic
--- Prednisone 1mg/kg (5-7days)
--- Plaquenil (hydroxychloroquine) 200 mg BID
126
Why does lichen planus have malignant potential?
* Mechanisms
--- Chronic inflammation
--- Immune dysregulation
--- Topical/Systemic immunosuppressants
* Risk (0.1-0.2%)
127
Three DD for this
mucous membrane pemphigoid
phephigus vulgrais
lichen planus
128
Where in the epithelium do these occur?
Pemphigus Vulgaris
Bullous Pemphigoid
Mucous Membrane Pemphigoid
Paraneoplastic Pemphigus
intraepithelial
- Pemphigus Vulgaris
- Paraneoplastic Pemphigus
sub-epithelial
- Bullous Pemphigoid
- Mucous Membrane Pemphigoid
129
What is pemphigus vulgaris (PV)?
* Autoimmune vesicullobullous condition
* 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
130
What are the clinical features of pemphigus vulgaris?
Nikolsky sign
* application of firm lateral pressure on normal-appearing mucosa adjacent to a pre-existing bulla induces new bulla formation
Asboe-Hansen sign
* application of pressure directly to a bulla causes lateral extension
131
What are the oral features of pemphigus vulgaris?
* “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
132
What is the pathogenesis of pemphigus vulgaris?
- pemphigus (desmoglein 3 of desmosome)
133
What is the histopathology of 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
134
What are the three conditions have that Tzanck cells?
- pemphigus vulgaris
- erythema multiforme
- herpes
135
What does immunofluorescence show on pemphigus vulgaris?
* DIF
--- Intercellular IgG/IgM ±C3
* InDIF & ELISA
--- +ve in 80-90% cases
--- circulating autoantibodies
| chicken wire
136
What is the management of pemphigus vulgaris?
* Better prognosis/control if dx early
--- before devof corticosteroid tx 60-90% died due to dehydration, electrolyte imbalances, malnutrition & infection
- Prednisone
--- 5-10% mortality rate now due to complications of long-term corticosteroid use
--- alternate day prednisone plus steroid sparing immunosuppressant
* Steroid-sparing agents
* Monitor circulating autoantibody titres via inDIF to gauge success of tx
* 75% pts have disease resolution 10 yrs s/p tx
137
What is bullous pemphigoid (BP)?
* Most common autoimmune blistering condition
--- 1 in 100,000 annually
* Age: 6th-8th decade
* Gender: 2:1 male
* Oral involvement is uncommon
138
bullous pemphigoid (BP)
139
What is the histopathology of bullous pemphigoid?
Perilesional biopsy
* subepithelial separation
* eosinophils within bulla
* acute & chronic inflammatory cells
140
What is seen on the direct innumofluorescence of bullous pemphigoid?
* BMZ
--- linear IgG & C3 (90-100%)
* Hemidesmosomes
--- BP180 (lamina lucida)
--- BP230
| hemidesmosomes
141
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
--- Dapsone
--- Tetracycline
--- Niacinamide
* Refractory cases
--- Prednisone & Cyclophosphamide
142
What is mucous membrane pemphigoid (MMP)?
* 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
143
What are the subtypes of mucous membrane pemphigoid?
* Ocular involvement only
* Oral involvement only
* Mucosal & cutaneous involvement
* Multiple mucosal sites without cutaneous involvement
144
mucous membrane pemphigoid (MMP)
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What are the types of ocular complications with mucous membrane pemphigoid?
- 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
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If you treat someone with steroids does that affect the biopsy?
YES
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What does the histopathology look for mucous membrane pemphigoid?
Perilesional biopsy
* BM separation
* subepithelial clefting
* inflammatory infiltrate superficial lamina propria
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What does the direct immunofluorescence look for mucous membrane pemphigoid?
Perilesional biopsy
- linear band IgG & C3 (90%)
- IgA & IgM (more severe)
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What is the management for mucous membrane pemphigoid?
- 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
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What is paraneoplastic pemphigus (PNP)?
* 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%)
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What is the pathogenesis of paraneoplastic pemphigus (PNP)?
* 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
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What are the clinical features of paraneoplastic pemphigus (PNP)?
* PNP developed prior to malignancy dx
--- 1/3 of reported cases
* Signs & Symptoms
--- sudden appearance
--- polymorphous
* Cutaneous lesions
--- bullae -> erosions -> target lesions -> lichenoid lesions -> erythematous papules
---papular& pruritic ( cutaneous LP)
--- palmar or plantar bullae (uncommon in PV)
- Vagina, respiratory tract, oral & conjunctival mucosa (scarring similar to MMP)
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What are the oral manifestations of paraneoplastic pemphigus (PNP)?
“Erythema multiformelike stomatitis”
* Hemorrhagic lip crusting
* All sites
* Oral involvement only in some cases
* Multiple painful irregular ulcers
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What is the histopathology of paraneoplastic pemphigus (PNP)?
Non-specific
* lichenoid mucositis
* intraepithelial clefting
* subepithelial clefting
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What is the direct immunofluorescence of paraneoplastic pemphigus (PNP)?
* Weakly +ve linear IgG/C3 along intracellularly & BMZ
* InDIF
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What is the immunoblotting of paraneoplastic pemphigus (PNP)?
* Considered the **gold standard** for PNP diagnosis
* Characteristic reactivity with two plakin proteins is highly sensitive and specific for PNP
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What is the management for paraneoplastic pemphigus (PNP)?
* 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
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What is the summary of DIF, inDIF, and target antigens in the vesiculobullous Conditions?
