Immune-Mediated Diseases Affecting Oral Mucosa Flashcards
1
Q
Recurrent apthous stomatitis is a synonym for…
A
“canker sores”
2
Q
Painful ulcers with red halo
A
Recurrent aphtous stomatitis, or “canker sores”
3
Q
___% of the population are afflicted with canker sores
A
20%
4
Q
Pathogenesis of recurrent aphthous stomatitis
A
- common manifestation of many disease processes, each mediated through immune system
- epithelial destruction due to TNF-alpha generated by T cells, macrophages and mast cells
5
Q
Epithelial destruction in recurrent aphthous stomatitis is due to…
A
TNF-alpha generated by T-cells, macrophages, and mast cells
6
Q
Proposed etiologic factors of recurrent aphthous stomatitis
A
- Allergies
- Nutritional deficiences
- Genetic predisposition
- Hematologic factors
- Hormonal factors
- Infections
- Stress
- Trauma
7
Q
3 categories of proposed etiologic factors
A
- Primary immunodysregulation
- Decreased mucosal barrier
- Increased antigenic exposure
8
Q
Minor aphthous ulcers make up what percentage of RAU cases?
A
> 80% RAU cases
9
Q
Major aphthous ulcers make up what percentage of RAU cases?
A
~10% RAU cases
10
Q
Size of minor aphthous ulcer vs major aphthous ulcers
A
- Minor is < one cm in diameter
* Major is larger
11
Q
Shape of minor aphthous ulcer vs major aphthous ulcers
A
- Minor is symmetrical
* Major has an irregular shape
12
Q
Timeline of resolution of a minor and major aphthous ulcer
A
- Minor resolves in 2 weeks
* Major persists up to 6 weeks
13
Q
Healing outcome of minor vs major aphthous ulcer
A
- Minor aphthous ulcers heals w/o scarring
* Major aphthous ulcers heals with scarring
14
Q
Quantity of lesions in minor and major aphthous ulcers
A
- Minor has fewer lesions than in major
* Major has more lesions than in minor
15
Q
Location of minor and major aphthous ulcers
A
- Minor occurs in lining mucosa
* Major occurs most in lining mucosa
16
Q
Minor aphthous ulcers
A
- Prodromal burning or itching
- Erythematous macule
- Fibrinopurulent membrane with red halo
- 1-5 lesions/episode
17
Q
Major aphthous ulcers are also called…
A
- Sutton’s Disease
* Periadenitis Mucosa Necrotica Recurrens
18
Q
Major aphthous ulcers
A
- Deeper and more painful than minor form
- Any oral site but more on lining mucosa
- 1-10 lesions/episode
- DDx includes squamous cell carcinoma
- Scarring rarely –> restricted mouth opening
19
Q
Herpetiform aphthous ulcers
A
- Least common type
- 1-3 mm
- < 100 ulcers/episode
- Heal 7-14 days
- Most frequent recurrences
- Any oral site, but more common on lining mucosa
20
Q
Simple aphthosis
A
- Few lesions
- Heal in 2 weeks
- Few recurrences
21
Q
Complex aphthosis
A
- Multiple lesions
- Rapid recurrences
- Severe pain
- +/- genital or perianal lesions
22
Q
Diagnosis of recurrent aphthous ulcers
A
- Clinical criteria
- Histology: non-specific ulcer
- Biopsy excludes other diagnoses
23
Q
The following conditions must be ruled out in the diagnosis of recurrent aphthous ulcers…
A
- Hematologic deficiency
- GI disease
- Immunodeficiency
- Drug reaction
24
Q
Management of simple aphthosis
A
Topical treatment:
• OTC anesthetics
• Topical corticosteroids
25
Management of complex aphthosis
Rule out systemic disease:
• More potent topical corticosteroids
• Injected corticosteroids
• Cyclic neutropenia
26
Disorders associated with oral aphthous ulcers
* Behcet's syndrome
* Reiter's syndrome
* Immunocompromised conditions (HIV)
* CIBD (Crohn's & Ulcerative colitis)
* Nutritional deficiencies
* Celiac disease
* Cyclic neutropenia
27
Behcet's syndrome (disease)
* "Chronic ocular inflammation + orogenital ulcers"
* Actually multisystem disease
* Immunodysregulation
* Possible genetic predisposition
* Rare in most countries
28
Environmental antigens that trigger Behcet's Syndrome
* Bacteria (streptococci)
* Viruses
* Pesticides
* Heavy metals
29
Histocompatibility antigen associated with Behcet's syndrome
Histocompatibility antigen B-51 (HLA-B51) link
30
Common in Japan, Middle East
Behcet's and HLA-B51
31
Diagnosis of Behcet's Syndrome
```
• Oral aphthous ulcers - 3 recurrences per year
• PLUS 2 of 4:
- Genital lesions
- Ocular lesions
- Cutaneous lesions
- Pathergy
```
32
Histology of Behcet's Syndrome
• Similar to aphthous ulcers
- T lymphocytes prominent
• Leucoytoclastic vasculitis
- Neutrophil attack on small artery walls
- Karyorrhexis of neutrophils
- Fibrinoid: smudy fibrin-like deposits of degenerated collagen or ground sub in arterial walls
33
Treatment for Behcet's Syndrome
```
• Corticosteroids
• Immunomodulators
- Imuran
- Cyclophosphamide
- Cyclosporine
- Methotrexate
```
34
Prognosis of Behcet's Syndrome
```
• Variable
• Fewer attacks
• Prognosis good unless:
- CNS disease
- Severe vascular changes
```
35
Common chronic skin condition (affects approximately 1.5 million Americans)
Psoriasis
36
Etiology of psoriasis
• Immunologic factors
- TNF etc. causes keratinocyte proliferation
• Lesions coincide with T-cell infiltration into epidermis
• Genetic factors
37
Clinical features of Psoriasis
• Starts age 10 to 30 years
• Persists for years
• Worse in winter
• Symmetrical distribution on scalp, elbows, knees
• Well-defined erythematous plaques with silvery scale
- May itch, be painful, and can bleed
• Arthritis in 10%
• Oral lesions uncommon
- Red plaques
- Erythema migrans?
38
Well-defined erythematous plaques with silvery scale are observed in...
Psoriasis
Note: it may itch, be painful, and can bleed
39
Psoriasiform histologic pattern
* Parakeratosis
* Microabscesses
* Long rete ridges
* High connective tissue papillae
40
Psoriasis differential diagnosis
* Erythema migrans
* Reiter's syndrome
* Candidiasis
* Psoriasis
41
Synonyms for Erythema Migrans
* Geographic tongue
* Benign migratory glossitis
* Erythema areata migrans
* Psoriasiform mucositis
42
Clinical features of erythema migrans
* Multiple well-defined lesions
* Erythematous zone
* White or yellow slightly raised border
* +/- burning sensation
* Anterior 2/3 dorsal tongue > lining mucosa
* Atrophic filiform papillae
* Lesions enlarge, subside, appear elsewhere
* +/- fissured tongue
43
Demographics of erythema migrans
* Common
* F > M
* <3% of population
44
Etiology of erythema migrans
• Etiology unknown
• Possible hypersensitivity reaction
• Erythema migrans + psoriasis associated with HLA-Cw6?
- Similar histology
45
Histology of erythema migrans
Periphery:
• Hyperkeratosis
• Acanthosis
• Elongated rete ridges
Center:
• Intraepithelial microabscesses (neutrophils)
Lamina propria
• Acute and chronic inflammatory cells
46
Management of erythema migrans
* "Reassurance"
| * Topical corticosteroids
47
Demography of lichen planus
* Middle age onset
| * F slightly > M
48
What is lichen planus?
* Chronic immunologically-mediated disease
* Oral lesions +/- lesions on skin, other mucosae
* Oral lesions more persistent than skin lesions
49
Skin lesions of lichen planus
* Most on flexor surfaces
* Plaques or papules
* Purple, flat-topped with white (Wickham's) striae
* Pruritic
* Wax and wane and often subside in 2 years
50
Types of oral lesions in lichen planus
* White adherent
* Erosive
* Vericulobullous
51
White adherent oral lesion of lichen planus
```
• Asymptomatic
• Reticular striae
- Interlacing white lines
- Bilateral and symmetrical
- Buccal mucosa > tongue > gingivae
• Plaques
- Tongue and buccal mucosa
• Papules
```
52
Erosive (e.g. desquamative gingivitis) oral lesion of lichen planus
* Symptomatic
* Atrophic/Erythematous areas around central ulceration
* Ulcerations of varying degrees
* +/- peripheral white striae
* very rare malignant transformation
53
Which type of oral lesion of lichen planus is rare?
Vesiculobullous
54
Histology of lichen planus
• Orthokeratosis or parakeratosis
- Thickness of keratin correlates with clinical appearance
• Uneven acanthosis
• Rete ridges prominent, sharp ("saw tooth"), or absent
• T-lymphocyte zone in upper lamina propria
• Loss of basal cells
• Colloid, cytoid or Civette bodies
55
What are Civette bodies?
Apoptotic basal cells are eosinophilic degenerating keratinocytes
56
When are Civette bodies observed?
Lichen planus
57
What's observed in the immunofluorescence of Lichen planus?
* Nonspecific: shaggy fibrinogen band along BMZ
| * Globular deposits of IgM and complement on colloid bodies in some cases
58
Clinical differential diagnosis for Lichen Planus
```
• Hypersensitivity reactions
- Systemic (e.g. drugs)
- Local or contact (e.g. amalgam, cinnamon)
• Lupus erythematosus
• Chronic ulcerative stomatitis
• Oral graft-versus-host disease
```
59
Management of Lichen Planus
• Reticular
- No treatment needed after diagnosis
- Clinical monitoring
• Erosive
- Topical corticosteroids
- Systemic immunosuppressives if necessary
- Monitor for potential dysplasia, SCC
- Monitor for iatrogenic candidiasis
60
What is Lichenoid Mucositis?
* Lesions with clinical and/or histological resemblance to classical lichen planus
* May exhibit some variation from classical features
61
Types of pemphigus
* Vulgaris
* Vegetans
* Foliaceus*
* Erythematosus*
* Paraneoplastic
* Drug induced
* Do not affect oral cavity
62
Which types of pemphigus do not affect oral cavity?
* Foliaceus
| * Erythematosus
63
Clinical features of pemphigus vulgaris
* Autoimmune vesiculobullous mucocutaneous disease
* Appears first in mouth in some cases
* Childhood to old age, but most 30-50 years
* Flaccid lesions
* Nikolsky sign positive
* Painful
* Vesicles rupture rapidly to form irregularly-shaped ulcers as they spread peripherally and coalesce
64
What is a positive Nikolsky sign?
Firm lateral pressure on normal-appearing mucosa (or skin) produces a blister
65
Pemphix (Greek) means...
bubble or blister
66
Nikolsky sign positive in many cases of pemphigus and also in percentage of some other mucocutaneous conditions including...
* Pemphigus vulgaris
* Paraneoplastic pemphigus
* Pemphigoid (all types)
* Bullous lichen planus
* Erythema multiforme
* Hypersensitivity reactions
* Epidermolysis bullosa
67
Histology of pemphigus vulgaris
• Acantholysis
• Suprabasilar cleft with tombstone basal cells
- Cleft contains Tzanck cells
68
Diagnosis of pemphigus vulgaris
* Exfoliative cytology: acantholytic round epithelial (Tzanck) cells
* Perilesional biopsy
* Direct immunofluorescence: labeled Igs attach** to autoantibodies to desmogleins 1 and 3 arund epithelial cells in biopsy specimen. This creates a fishnet pattern.
* Indirect immunofluorescence: labelled circulating** autoantibodies to desmoglein 1 and 3 create same pattern on animal mucosa
69
Management of pemphigus vulgaris
* Diagnose as soon as possible
* Rule out drug reaction
* Medication should be prescribed by experienced physician
* Systemic corticosteroids
* Other immunosuppressive agents
* Monitor for iatrogenic candidiasis
* Monitor disease by I.I.F.
* 10% fatal due to medications
70
Drug reactions related to pemphigus...
* A variety of drugs have been implicated in the onset of drug-induced pemphigus
* Some of these drugs induce antibody formation, which results in acantholysis via a mechanism identical to that found in idiopathic pemphigus.
* Other drugs are posulated to induce acantholysis directly in the absence of antibody formation
71
Side effects of systemic corticosteroids in pemphigus...
* Diabetes mellitus
* Adrenal suppression
* Weight gain
* Osteoporosis
* Peptic ulcers
* Severe mood swings
* Increased susceptibility to infections
72
Circulating Igs correlate with disease activity in...
* I.I.F. used to monitor disease
| * Pemphigus
73
Pemphigus vegetans
• Variant of pemphigus vulgaris
• Oral involvement in a few cases
• Acantholytic bullae are followed by epithelial hyperplasia and intraepithelial abscess
- Eosinophils within the abscesses
• Pustular vegetations may look verrucous
• Vegetans type may occur in lull in pemphigus vulgaris
• Can spontaneously remit
74
Mucocutaneous disease associated with lymphoma or benign lymphoproliferative disease
Paraneoplastic pemphigus
75
May appear before lymphoma is diagnosed...
paraneoplastic pemphigus
76
Clinical presentation of paraneoplastic pemphigus
* Sudden onset of multiple vesiculobullous lesions on skin and mucosae
* Cicatricial conjunctivitis in some cases
* Skin lesions papular and pruritic (like lichen planus)
* Lips resemble erythema muliforma (crusting)
77
Corticosteroid controls this disease but makes malignancy worse...
Paraneoplastic pemphigus
78
Pathogenesis of paraneoplastic pemphigus
* Igs against intercellular and basement membrane zone antigens
* Tumor --> host lymphocytes --> IL-6
* Cytotoxic T lymphocytes
* This multifaceted immunologic attack produces variety of clinical, histological & immunological changes
79
In paraneoplastic pemphigus, IL-___ stimulates Igs against...
IL-6 stimulates Igs against:
• Desmosomal antigens
• Basement membrane zone antigens
80
Histology of paraneoplastic pemphigus
• Lichenoid mucositis with subepithelial cleft or intraepithelial cleft
- Some cases are only lichenoid
• Immunoprecipitation studies: antibodies against desmoglein 1 and 3, desmoplakin I and II, BPAG1
81
Immunoprecipitation studies in paraneoplastic pemphigus show antibodies against...
* Desmoglein 1 and 3
* Desmoplakin I and II
* BPAG1
82
Demographic of mucous membrane pemphigoid
Most often affects females, especially those over 40 years of age
83
Mucous membrane pemphigoid clinical features
* Chronic vesiculobullous disease
* Vesicles rupture: painful ulcers may persist for months
* One cause of desquamative gingivitis
* Conjunctival involvement may --> scarring
84
Nikolsky sign for mucous membrane pemphigoid
Positive
85
Where can mucous membrane pemphigoid occur?
Any part of oral mucosa, other mucosae, (skin)
86
Describe the conjunctival involvement in mucous membrane pemphigoid
Conjunctival involvement may --> scarring:
• Symblepharon: adhesions between bulbar and palpebral conjunctivae
• Ankyloblepharon: adhesion of ciliary edges of eyelids to each other
• Entropion: scarrying may --> eyelids turn inwards
87
Pathogenesis and histology of mucous membrane pemphigoid
* Autoantibodies (IgG) to BMZ antigens
* Binding of IgG triggers a reaction involving complement and neutrophils
* Weakens basement membrane
88
Discuss autoantibodies to BMZ antigens involved in mucous membrane pemphigoid
Hemidesmosome:
• BPAG1 (230kd) in plaque
• BPAG2 (180kd) transmembrane protein
• Integrin α6β4
Laminda lucida:
• Laminin (epiligrin) in anchoring filaments
89
Immunofluorescence of mucous membrane pemphigoid
• Homogenous linear fluorescence at basement membrane zone on D.I.F.
- IgG, C3, etc.
• Circulating Ig's (I.I.F.) in only 5-30% cases
90
Differential diagnosis of mucous membrane pemphigoid (subepithelial vesicles in oral vesiculo-ulcers)
* Pemphigoid (all types)
* Epidermolysis bullosa (some types)
* Linear IgA disease
* Angina bullosa hemorrhagica
* Dermatitis herpetiformis
91
Management of mucous membrane pemphigoid
```
• Rule out drug induced disease
• Ophthalmic consult
• Topical corticosteroids
- Increase potency as necessary
• Systemic
- Corticosteroids
- Steroid sparing immunosuppressives
- Tetracycline or minocycline
- Dapsone
```
92
What is desquamative gingivitis?
* Gingivae red, edematous, and glazed
* Superficial ulceration or desquamation/peeling
* Buccal > lingual
93
Desquamative gingivitis occurs in various vesiculobullous conditions including...
* Mucous membrane pemphigoid
* Erosive lichen planus
* Chronic ulcerative stomatitis
* Pemphigus vulgaris
* Drug reactions
* Epidermolysis bullosa acquisita
* Systemic lupus erythematosus
* Linear IgA disease
94
Most common A-I blistering disease
Bullous pemphigoid
95
Demography of bullous pemphigoid
Older people (60-80)
96
Clinical presentation of bullous pemphigoid
* Starts with pruritus
* Multiple tense bullae on normal or erythematous skin
* Bullae rupture producing crust
* Heal w/o scars
97
Clinical course of bullous pemphigoid in relation to mucous membrane pemphigoid
Clinical course shorter than MMP
98
How common are oral lesions in bullous pemphigoid?
Oral lesions uncommon (~15%)
99
Histology of bullous pemphigoid
* Subepithelial cleavage
| * Eosinophils within bullae
100
Antigens involved in bullous pemphigoid
Antigens: BP 180 and BP 230
101
Immunofluorescence for bullous pemphigoid
* D.I.F. positive in 90% to 100%
| * I.I.F. positive in 50% to 90%
102
What do titers in bullous pemphigoid indicate about the disease activity?
Titers don't correlate with disease activity.
103
Management of bullous pemphigoid
* R/o drug-induced disease
* Systemic immunosuppressive agents
* Lower doses of prednisone than for pemphigus
* Better prognosis
* Reported spontaneous remission in 2-5 years in some cases
* Mortality due to treatment in older patients
104
Pathogenesis of systemic lupus erythematosus
```
• Genetic, environmental and hormonal factors trigger:
- Increased B cell function
- Abnormal T cell activity
• Antibodies against host cell antigens:
- Nuclear
- Cytoplasmic
- Cell surface
```
105
Clinical features of systemic lupus erythematosus
* Young adult females
* Erythematous cutaneous rash ("butterfly" pattern on face)
* Fever, weight loss, malaise
* Glomerulonephritis
* Damage to: Joints, Heart, Lungs
106
Erythematous cutaneous rash, or "butterfly" pattern on face is indicative of...
Systemic lupus erythematosus
107
Oral lesions found in SLE
* White plaques +/- ulceration
* Erythema/Erosions/Ulcers
* Desquamative gingivitis
* Classical lesion: central red area or ulcer with white spots and peripheral radiating white lines
* Oral lesions may occur in SLE and CCLE
108
This classical lesion is associated with what? --> Central red area or ulcer with white spots and peripheral radiating white lines
Systemic Lupus Erythematosus
109
Laboratory abnormalities observed in SLE...
```
• Hematologic changes:
- Anemia
- Leukopenia (decrease in WBC)
- Thrombocytopenia (decrease in thrombocytes)
• Reduced serum complement concentration
• Antinuclear antibodies (ANAs)
```
110
What is the most common technique to detect antinuclear antibodies (ANAs) in SLE?
Indirect immunofluorescence
111
What does the pattern of nuclear fluorescence indicate in SLE?
Pattern of nuclear fluorescence suggests the type of antibody.
112
SLE: homogenous/diffuse pattern of nuclear fluorescence
antibodies to chromatin, histones, and ds-DNA
113
SLE: rim pattern of nuclear fluorescence
antibodies to ds-DNA
114
SLE: specked pattern of nuclear fluorescence
```
Antibodies to non-DNA antigens (histones and RNP):
• Sm
• RNP
• SS-A (Ro)
• SS-B (La)
```
115
SLE: nucleolar pattern of nuclear fluorescence
antibodies to nucleolar RNP
116
Histology of SLE
• Hyperkeratosis
- Follicle keratin plugging in skin in CCLE (Chronic cutaneous lupus) but not in SLE
• Alternating epithelial atrophy/acanthosis
• Basal cell degeneration (apoptotic bodies)
• Subepithelial edema (+/- vesicles)
• Thick PAS-positive basement membrane zone
• Subepithelial vascular and adnexal lymphocytes
117
Immunofluorescence results for SLE and CCLE
• I.F. shows shaggy, granular-linear deposits in band along mucocutaneous basement membrane zone
- IgG (IgM & IgA), C3, and fibrinogen
- Band along basement membrane zone is lupus band test
- Positive in clinically normal skin in SLE (not in CCLE)
118
Pathogenesis of systemic sclerosis
Probably autoimmune pathogenesis
119
What is systemic sclerosis and its clinical presentation?
* Increased collagen deposition
* Insidious onset
* Fibrosis of lungs, heart, kidneys, GI tract, skin
* Interstitial pulmonary disease --> secondary pulmonary hypertension --> right-sided heart failure
* Sclerodactyly: symmetrical thickening, tightening and induration of skin of fingers and toes
120
Demography of systemic sclerosis
Females affected more than males
121
Disease characterized by increased collagen deposition
Systemic sclerosis
122
What is Raynaud's phenomenon?
• Arterial insufficiency of acral parts secondary to another disorder that causes arterial narrowing:
- SLE, systemic sclerosis, etc.
• Claudication (limping), color and temperature changes
• Chronic ulcerations and eventual gangrene
• In Raynaud's disease, vasospasm and its consequences are primary (increased response to stimuli has no known cause)
123
Histology of systemic sclerosis...
Dense collagen replaces and destroys normal tissue
124
Serology of Systemic Sclerosis
• Rheumatoid factors (RF) is antibody against Fc fragment of human IgG
• ANAs:
- Anti-Scl-70 (antibodies to topoisomerase I)
- Anticentromere antibodies
- No evidence that humoral immunity plays a significant role in pathogenesis, but these two ANAs are virtually unique to this disease and anti-Scl-70 is a marker for development of more aggressive disease
125
What medication may inhibit collagen formation in systemic sclerosis?
D-penicillamine
126
Additional management for systemic sclerosis
• Surgery
• Esophageal dilation
• Calcium channel blockers
- Increase peripheral blood flow and reduce Raynaud's changes
• ACE (Angiotensin converting enzyme) inhibitors
- Reduce hypertension if kidneys severely affected
• Oral hygiene instruction
• Poor long-term prognosis
127
What is Crest syndrome?
Mild form of systemic sclerosis
128
Demography of crest syndrome
50-70 year old females
129
Symptoms of crest syndrome
* Calcinosis cutis
* Raynaud's phenomenon
* Esophageal dysfunction
* Sclerodactyly
* Telangiectasia
130
What is erythema multiforme?
* Ulcerative mucocutaneous disease
* "Self-limiting" hypersensitivity reaction
* Acute, chronic, or recurring acute
131
Types of erythema multiforme...
```
• Erythema multiforme minor
• Erythema multiforme major
- Stevens-Johnson syndrome
• Toxic epidermal necrolysis (TEN)
- Lyell's disease
```
132
Pathogenesis for erythema multiforme
• Uncertain
• Immunologically mediated
• Some immunologic precipitating/triggering events
- Infections: HSV, Mycoplasma pneumoniae
133
Demography of erythema multiforme minor
* Young adults
| * Males affected more often than females
134
Clinical presentation of erythema multiforme minor
Abrupt onset:
• Some cases chronic
• Some cases recurrent (linked to HSV)
Prodrome: fever, malaise, headache
135
Oral lesions observed in erythema multiforme minor
```
• Pain
- Mild to severe
- May --> dehydration
• Erythematous patches
- Epithelial necrosis
• Aphthous-type ulcers
• Multiple superficial extensive irregular ulcers
• Some vesicles/bullae
- Soon rupture
• Lips affected more than other sites. Gingivae less affected than other sites
- Hemorrhagic lips
```
136
Which sites in oral lesions from erythema multiforme minor are affected?
Lips affected more than other sites. Gingivae less affected than other sites.
137
Skin lesions observed in erythema multiforme?
* Target lesions: concentric erythematous rings
| * Macules, papules, vesicles, bullae, etc.
138
Resolution of erythema multiforme minor
Usually resolves spontaneously in 2-6 weeks
139
Erythema multiforme major is also known as...
Stevens-Johnson syndrome
140
Clinical presentation of erythema multiforme major
* Oral, eye, and genital lesions
* Symblepharon may occur
* Often drug induced
141
Mortality rate for those with erythema multiforme?
~2-10% mortality
142
Toxic epidermal necrolysis (TEN) is also known as....
Lyell's disease
143
Etiology of toxic epidermal necrolysis (TEN)...
Usually drug induced
144
Clinical presentation of toxic epidermal necrolysis
* Sloughing and ulceration of entire skin and mucosae
| * Resembles burn victim
145
How long does it take skin & oral lesions to resolve in someone with toxic epidermal necrolysis?
Skin lesions resolve in less than 4 weeks. Oral takes longer.
146
Percent mortality rate for toxic epidermal necrolysis (TEN)
~34% mortality
147
Histology of erythema multiforme
```
• Necrotic keratinocytes
• Spongiosis
• Vesicles in epithelium may extend below the epithelium
• Interface infiltrate
- Lymphocytes, neutrophils
- +/- eosinophils
• Perivascular inflammation
```
148
Histology is characteristic, but not pathognomonic for this disease...
Erythema multiforme
149
Immunofluorescence for erythema multiforme is...
non-specific
150
Describe corticosteroid treatment for erythema multiforme
• Corticosteroid use is controversial
- Effectiveness is questionable
- May be dangerous in TEN
151
Management of erythema multiforme
• Bland mouthwashes may be adequate in erythema minor
• Eliminate triggers
- Antiviral agents in cases triggered by HSV
• Rehydrate (IV if necessary)
152
Treatment for toxic epidermal necrolysis
• Treated in burn unit
• Intravenous pooled human Ig
- Blocks Fas ligand
- which induces epithelial cell apoptosis
153
What is reactive arthritis/Reiter's syndrome?
• Abnormal immune reaction to microbial antigen (STD or dysentery)
154
Demography of reactive arthritis/Reiter's syndrome?
Young adult white males
155
Reactive arthritis/Reiter's syndrome associated with this pehnotype...
HLA-B27 phenotype
156
Clinical presentation of reactive arthritis/Reiter's syndrome...
```
• 1-4 weeks after exposure
• Acute onset of triad:
- Non-specific urethritis
- Conjunctivitis
- Arthritis
• Oral in fewer than 20%
- Ulcers (RAU)
- Papules
- Erythema migrans
• Skin lesions in some:
- Histology is psoriasiform
```
157
Management of reactive arthritis/Reiter's syndrome
NSAIDs for arthritis
158
Resolution of reactive arthritis/Reiter's syndrome
Lasts weeks to months with recurrence
159
Skin lesions that present in reactive arthritis/Reiter's syndrome show this type of histology...
Histology is psoriasiform
160
Timeline of acute graft v host disease and chronic graft v host disease
* Acute: within first 100 days of transplant
| * Chronic: continuation of acute GVHD or starts later than 100 days
161
How many bone marrow recipients are affected by AGVHD and CGVHD?
* Acute: affects 50% bone marrow recipients
| * Chronic: in up to 60% of bone marrow recipients
162
Clinical presentation of acute graft v host disease
* Skin mild to severe like "TEN"
| * Severe GI symptoms and liver dysfunction
163
Clinical presentation of chronic graft v host disease
* Mimics autoimmune diseases (SLE, Sjogren, etc.)
| * Skin changes resemble lichen planus or systemic sclerosis
164
In what percentage of chronic and acute graft v host disease are oral changes observed in..?
* In 33 to 75% of acute GVHD
| * In ~80% of chronic GVHD
165
Describe oral changes observed in GVHD
• Lichenoid appearance:
- Histology resembles lichen planus but inflammatory response is not as intense
- With advanced cases, collagen deposition resembles systemic sclerosis
• Burning
• 2nd candidiasis
• Ulcers
• Xerostomia
166
What is xerostomia?
Immune destruction of salivary glands
167
Histology of oral changes observed in GVHD resembles...
lichen planus, however, the inflammatory response is not as intense
168
Describe xerostomia as it relates to GVHD
Minor glands show periductal inflammation in early stages, with gradual acinar destruction and periductal fibrosis later
169
What does direct immunofluorescence identify?
Identifies factors in patient TISSUE
170
Describe direct immunofluorescence process
• Patient tissue incubated with F-labeled antibody against:
- Tissue bound autoantibody
- Tissue antigen (C3, fibrinogen)
- Foreign antigen (viral antigen)
171
What does indirect immunofluorescence identify?
Identifies autoantibody in patient SERUM
172
Describe indirect immunofluorescence process
* Animal mucosa incubated with patient serum
* Autoantibody (if present) in serum attaches to corresponding structure in mucosa
* Incubated with F-labeled antibody against autoantibody
