Lecture 12 - Immune System In Cutaneous Diseases Flashcards
1
Q
Immunological cell behavior in skin
A
- Langerhans cell sample the space for foreign antigens
- Dermal dendritic cells are migratory
2
Q
Neutrophils and inflammation
A
- participate in clearing of dead cells and pathogens
- potentially amage tissue by releasing toxic mediators
- release proinflammatory cytokines
3
Q
4 types of cutaneous hypersensitivity
A
- Type I: IgE mediated (anaphylaxis, urticaria)
- Type II: Antibody-mediated (Bullous diseases)
- Type III: Immune complex (Vasculitis)
- Type IV: Cell mediated (CHS, DTH)
4
Q
Type I hypersensitivity
A
- anaphylaxis
- urticaria
- angioedema
- things that make mast cells degranulate
5
Q
Urticaria classification and types
A
- Acute vs chronic (6 weeks +)
- spontaneous vs induced
- allergic (drug, infections, food)
- contact (allergic)
- physical (elicited by external stimuli: pressure, cold, heat, solar, vibrations)
- cholinergic urticaria (elicited by increase in core body temp)
6
Q
Acute urticaria
A
- very common
- post viral, particularly in children
- various identifiable allergens
7
Q
Direct mast cell degranulation can be caused by
A
- Curare/ D- tubocurarine
- opiates
- radiocontrast
- alcohol
- ASpirin, NSAID
8
Q
Chronic urticaria
A
- spontaneous vs inducible
- spontaneous: Due to known cause or due to unknown cause
- Inducible: physical, cholinergic, contact, aquagenic
9
Q
Prevalence of chronic spontaneous urticaria
A
- 0.5-1%
- Europe: 8 million
- world: 80 million
10
Q
Differential diagnosis of urticaria
A
- erythema multiforme
- urticarial vasculitis
- urticaria pigmentosa
- Rare syndromes
- Eosinophilic cellulitis
11
Q
Wheals
REcurret unexplained fever, joint pain, malaise
- autoinflammatory disease suspected
A
- Acquired hereditary AID
12
Q
- wheals/angioedema
- no fever, malaise or joint pain
- average wheel druation more than 24 hours
- signs of vasculitis in biopsy
A
- urticarial vasculitis
13
Q
- no recurrent unexplained fever or joint pain or malase
- average wheal duration
A
- chronic spontaneous urticaria
14
Q
- no recurrent unexplained fever or joint pain or malase
- average wheal duration
A
- chronic inducible urticaria
15
Q
- Angioedema
- ACE inhibitor treatment
- remission after stop
A
- ACE-Inh induced AE
16
Q
- Angioedema
- no ACE inhibitor treatment
- HAE or AAE suspected
A
- HAE I-III AAE
17
Q
Ruling out severe inflammatory disease
A
- ESR
- CRP
- differential blood count
18
Q
Causes of CSU
A
- autoreactivity (20%)
- infection (26%)
- intolerance (38%)
- other casues (2%)
- unknown
19
Q
History for CSU
A
- otherwise well?
- recent travel?
- pattern of urticaria?
- how long do individual lesions last?
- accompanying symptoms?
- precipitating factors
20
Q
Investigation of CSU
A
- FBC, ESR, differential
- EUC, LFT, hepatitis serology
- ANA
- Hep B
- Stool
- biopsy
- Food diary, dietary provocation test
- prick testing not helpful
21
Q
Treatment of urticaria
A
- avoid precipitating factors and direct mast cells degranulators
- treat underlying abnormalities
22
Q
Symptomatic Urticaria therapy
A
- second generation H1-Antihistamine (sgAH)
- if symptoms persist after 2 weeks
- Increase sgAH dose (up to 4 times)
- If symptoms persist after 1-4 weels
- add omalizumab, cyclosporine A or leukotriene antagonist
23
Q
- olizumab
A
- give an autoallergen to block IgE from binding Mast cells
24
Q
Type II/III hypersensitivity
A
- antibody/antibody-complex mediated
- organ speficic: thyrotoxicosis, pernicious anemia, Addison’s, goodpasture
- Middle: pemphigus, pemphigoid, myasthenia gravis, ITP
- Organ non-specific: Sjogrens, SLE, RA, sleroderma
25
Q
Pemphigus
A
- Antibodies against intercellular cement susbtance: keratinocytes lose touch
- intra-epidermal disruption: flaccid blisters and erosions
- Mucous membrane involvement usually prominent (60% present with oral disease alone)
- other mucosae
26
Q
Pemphigus group
A
- vulgaris (anti-desmoglein 3 and 1 antibodies)
- Foliaceus (anti-desmoglein 1 antibodies)
- erythematosus
- drug induced (Penicillamine, captopril)
- paraneoplastic
- pemphigus disrupts the desmosome
27
Q
- Treatment of pemphigus
A
- stop any causative drugs
- oral corticosteroids
- poisonsL steroid sparing drugs (Azathiprine, cyclophosphamide, methotrexate, cyclosporin)
- IVIG
- Plasmapheresis
- Rituximab (anti-CD20)
28
Q
Other bullous disorders
A
- pemphigus group
- bullous pemphigoid and pemphigoid gestionis:
- epidermolysis bullosa acquisita
- linear IgA dermatosis
- dermatitis herpetiformis
29
Q
Bullous pemphigoid
A
- disrupts attachment to the basement membrane
- very itchy disease
- histology: subepidermal blister formation and an inflammatory infiltrate composed of neutrophils and eosinophils in the dermis and bukllla cavity
30
Q
Treatment of bullous pemphigoid
A
- oral corticosteroids
- poisons
- IVIG
- PLasmapheresis
- Rituximab (anti-CD20)
31
Q
Type III hypersensitivity
A
- allergic vasculitis
- leukocytoclastic vasculitis
- polyareteritis nodosa
- usually in the legs
32
Q
Causes of small vessel vasculitis
A
- Infection
- Drugs (antibiotics)
- autoimmune (SLE, RA, others…)
- Malignancy: solid or lymphoproliferative)
- idiopathic: LCCV (60%)
33
Q
Investigations in vasculitis
A
- history
- fever, nodes, spleen
- investigate for cause/associations
- investigate for extent: check the kidneys
34
Q
Treatment of vasculitis
A
- remove antigen
- rest, warmth, compression stokings
- steroids
- NSAIDs
- Dapsone
- Colchicine
- immunosuppressants
35
Q
Type IV hypersensitivity
A
- Contact hypersensitivity (epicutaneous Ag)
- Delayed type hypersensitivity (intracutaneous Ag)
- granulomatous hypersensitivity (leprosy)
36
Q
Treatment
A
- identify antigen
- remove antigen
- steroids: topical, oral
37
Q
Atopic eczema
A
- involves both humoral and cell-mediated immunity
- IgE-mediated or T cell mediated allergies in many patients
- CD4+ (Th2) mediated inflammation in skin
- Skin barrier funciton disorder
38
Q
Atopic eczema
A
- Type I: IgE mediated allergies
- Type IV: house dust mite, pityrosporum yeasts, contact dermatitis to topical agents, staph toxins may act as superantigens
