Atopic disease Flashcards
What’s the difference between “atopy”, “atopic dermatitis”, and “atopic like dermatitis”?
Atopy refers to an individual who produces specific IgE antibodies following exposure to common environmental allergens, and is “sensitized” to that allergen.
Atopic dermatitis is a clinical syndrome that not all patients with atopy manifest.
Atopic-like dermatitis is an inflammatory and pruritic skin disease with clinical features identical to those seen in CAD in which an IgE response to an environmental or other alleged cannot be documented”. This acknowledges that IgEs are not necessary for manifestation of the disease.
T/F: some dog with clinical presentations of atopic dermatitis do not ave measurable IgE against environmental allergens.
T. some dogs that have typical clinical presentation of AD do not have measurable IgE against environmental allergens.
What is the hygiene theory?
decreased exposure to bacteria, parasites in conjunction with increased practices of excessive bathing and use of antibacterial detergents that can harshly affect the skin barrier may be responsible for the increased occurrence of AD.
These associations do not prove causality but do support that certain environmental factors may influence the development of CAD.
Which of these is the most recently discovered loss-of-function mutation in the human ___ gene, associated with abnormal epidermal differentiation?
A) R501X
B) 22Derf1
C) 2282derl14
d) RU486
Filaggrin gene;
A and B: R501X and 2282derl4
These mutations have been strong predisposing factors for early-onset extrinsic AD
T/F: Development of clinical disease of AD is not predicted by the level of IgE.
T. The development of clinical disease is not predicted by the level of IgE.
Which of these are not genes that have been investigated in canine AD?
a) Protein tyrosine phosphatase non receptor type 22
b) Kallikrein
c) Filaggrin
d) Melanin
d. Protein tyrosine phosphatase non receptor type 22 has been identified as a potential candidate gene for canine AD.
Kallikrein has been investigated, but unfortunately no significant association was identified.
A single-nucleotide polymorphism within Filaggrin in WHWT has been associated with CAD, but not in all dogs.
Which of these have shown structural defects in skin of dogs with AD?
a) Collagen VIII
b) Collagen IV
c) intercellular lipid lamellae
d) laminin 332
C; intercellular lipid lamella have exhibited structural defects in the stratum corneum of dogs with AD. Lamellar lipid delamination (“rollup”) was common as was widening of lipid lamellae in sensitized dogs.
T/F: Total IgEs are mildly different between normal and atopic dogs and a good way to differentiate an atopic dog from a normal one.
F; Total IgEs are nor significantly different between normal and atopic dogs.
T/F: Total IgEs are mildly different between normal and atopic dogs and a good way to differentiate an atopic dog from a normal one.
F; Total IgEs are nor significantly different between normal and atopic dogs. Allergen-specific IgGs occur in both normal and atopic dogs.
What are the two types of IgE that are proposed to exist, and which is hypothesized to cause disease and which is non pathogenic?
IgE+: causing disease
IgE-: not pathogenic
Discuss the biphasic pattern of cytokine expression that appears to be a critical determinant in AD lesions of both humans and mouse models:
Acute skin lesions: CD4+ TH2 lymphocytes, eosinophils, release of IL-4, IL-13. These lead to high IgE levels and increased survival and maturation of eosinophils. Th2 cells preferentially express CCR3, CCR4, CCR8. In humans, chemotaxis of cells expression CCR4 is induced by TARC, resulting in selective migration of Th2 cells into the skin. IL-6 has been shown to play a role in early reactions followed by an increase in IL-13 and TARC. Th2-cell subsets are activated during the initiation phase.
Chronic lesions show predominance of macrophages and are associated with TH1 type cytokines (IL-2, IL-12, IFN-gamma, IL-18). Th1 cells predominantly express CCR5, CXCR3. Th1-cell subsets are activated after Th2, to account for the persistence of inflammation.
Which of these chemokine have been found at increased levels in both cutaneous lesions of AD and sera of affected patients:
a) Regulated on activation, normal T-cell expresses and secreted (RANTES)
b) Monocyte chemoattractant protein-4 (MCP-4)
c) Eotaxin
d) Macrophage-derived chemokine (MDC)
e) Thymus and activation-regulated chemokine (TARC)
f) all of the above
g) none of the above
F, all of the above.
CAD has been proposed to be associated with an increase/decrease of IL-4 and tolerance may be related to increase/decrease of TGF-b and increase/decrease of TARC and increase/decrease in IFN-gamma.
increase, increase, increase, decrease.
CAD has been proposed to be associated with an increase of IL-4 and tolerance may be related to increase of TGF-b and increase of TARC and decrease in IFN-gamma.
Which adhesion molecule has been increased in lesional skin of atopic dogs?
A) L-Selectin
B) LFA-1
C) P-selectin
D) ICAM-1
c) p-selectin. Upregulation of P-selectin was accompanied by signs of functional changes such as increased cell margination and membrane-associated protein expression.
Although expression of ICAM-1 and TNF-a was not enhanced in lesional vs nonlesional skin, there was a Trend toward a correlated up regulation of both molecules.
T/F: all dogs with elevated IgE levels benefit from antihistamines.
F, controversial. Correlation between histamine release and IgE levels is not clear-cut. The importance of histamine as a major mediator of canine AD is controversial.
Which of these have NOT been found to be increased in atopic skin? A) MHCII B) ICAM-1 C) Langerhans cells D) eosinophils E) alpha-beta T cells F) gamma-delta T cells
A) epidermal eosinophil microaggregates and langerhans cells have been found in personal atopic skin. there is an increased endothelial cell expression of ICAM-1 BUT NOT MHCII in atopic dogs. As in humans, there are increased numbers of alpha-beta T cells (type 2) in atopic individuals.
there are more gamma-delta T cells (type 1) in lesional skin of atopic dogs.
What percent of dogs diagnosed with CAFR have reportedly concurrent AD?
13-30% of dogs diagnosed with CAFR have been reported to have concurrent AD
Which of these are immunologic mechanisms by which toxins precipitate AD:
a) The role of super antigens in epithelial presentation of allergen to Th2 cells
b) promotion of Th2 skin inflammation
c) promotion of Th1 skin inflammation
d) IgG production
e) IgE production
f) t-regulatory cell subversion
g) Expansion and migration of skin-homing T cells
h) modulation of chemokines
i) IgE anti-superantigen production
A,B,E, F, G, H,I
-not C, D
A direct association between these toxins and severity of AD have been documented.
T/F: Staphylococcus pseudintermedius can behave as an allergen and elicit an IgE response.
T. Dogs with recurrent pyoderma secondary to atopy and idiopathic recurrent superficial pyoderma had significantly higher meal levels of serum anti staphylococcal IgE than other groups tested.
this supports that bacterial hypersensitivity may be responsible for initiations or perpetuating skin lesions in a subset of animals.
Also, penetration of staphylococcal antigens have been demonstrated and may be increased with degranulation of mast cells
T/F: Malassezia antigens can elicit a hypersensitivity response in atopic dogs.
T.
Why might allergen avoidance during puppyhood prevent development of IgE-mediated allergy in dogs?
Puppies born during allergy season, with pollen exposure in the first few months of life appear to be at increased risk for development of AD. IgE-mediated allergies require early allergen contact and sensitization for full development of sustained IgE levels. Allergen avoidance during early life may have some preventative effect on IgE mediated allergy in dogs.
According to the Task Force, which is the most commonly observed primary lesion in clinical AD?
a) alopecia
b) pustules
c) erythema
d) plaques
Erythema. But, some authors have reported the presence of primary macular to plaque-type eruptions or papular eruptions that are smaller than those expected to be seen with infection.
According to Willemse, what are the major features that can aid in diagnosis of canine atopic dermatitis?
pruritus
facial and/or digital involvement
lichenification of flexor surface of tarsus
extensor surface of carpus
chronic or chronically relapsing dermatitis
individual or familial history of atopy
breed predilection
According to Willemse, which are minor features that should also represent with at least 3 major features before diagnosing AD?
onset of signs before 3 yrs of age facial erythema and cheilitis bacterial conjunctivitis superficial staphylococcal pyoderma hyperhidrosis immediate skin test reactivity to inhalant allergens elected allergen specific IgGd Elevated allergen-specific IgE
What are the criteria for canine AD as proposed by Prelaud?
onset of signs under 3 yrs od age dog living mostly indoor glucocoritoic-responsive pruritus pruritus with lesions at onset affected front feet affected pinnae unaffected ear margins unaffected dorsal lumbar area
What are the criteria for canine AD as proposed by Favrot?
onset of clinical signs under 3 yrs of age glucocorticoid responsive pruritus affected front feet affected pinnae cheilitis
Ddx for atopy:
CAFR, contact allergy, FAD, internal parasitism with hypersensitivity, primary seborrhea, mycosis fungicides, drug eruption
To which family do D. farinae and D. pteronyssinus belong?
Pyrogliphidae
Which are the most important allergens in Europe?
house dust, house dust mite, human dander
Which is the most important allergen in the US and Japan?
house dust mite
___ is a glyciphagid house dust mite found in ___ climates.
Bloomia tropicalis, tropical and subtropical climates
What is the optimal histamine concentration for IDST?
1:10,000 w/v
List drugs that can interfere with IDST reactions
glucocorticoids, antihistamines tranquilizers, pro gestational compounds, hypotensive medications, narcotics (can cause nonimmunologic histamine release), irritant test allergens such as glycerin
Inappropriate sedatives include: oxymorphone, ket/val, acepromazine, propofol
Which sedatives and anesthetics are acceptable for intradermal skin testing?
xylazine, medetomidine, tiletamine/zolazepam, thiamylal, halothane, isoflurane, methoxyflurane
t/f: Cushingoid dogs should not have IDST performed until their HAC is under control.
F; hypercortisolemia did not change intradermal skin test reactions in previous studies
Late-phase reactions occur __ hours after testing
6 hours
Delated skin test site reactions should be evaluated ___ hours later.
24-48 hrs
What are the methodologies for serologic allergy testing?
RAST = radioallergosorbent test
ELISA
Liquid-phase immunoenzymatic assay (VARL)
All look for allergen-specific IgE, but this is a poor indicator of allergic status and should not be used as a diagnostic test.
Explain the principle of allergen-specific IgE assays:
serum is collected and allowed to react with allergen extracts.
Unbound antibodies are washed away, and those bound is detected using a reactant specific for IgE.
The IgE-specific reagents have been coupled to an enzyme or radioisotope that is then quantified by kilometric, fluorometric, or radiometric method. the amount of signal generated is proportional to the amount of allergen-specific IgE.
RAST and ELISA attach allergens to a solid substrate, but the liquid-phase mixes a labelled allergen with the serum.
