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The Veterinary Journal 171 (2006) 16–17
TheVeterinary Journal
Guest editorial
Atopic dermatitis in dogs – Hitting the moving target
Pruritus is one of the most common reasons that dogs
are presented to a veterinarian, other than routine care.There are many causes of pruritus but one of the most
common, if not the most common, is atopic dermatitis
(AD). Managing this incurable disease is frustrating to
both owners and their veterinarians.
The definition of AD in dogs has been evolving over
time and is currently defined by the American College of
Veterinary Dermatology task force on canine atopic
dermatitis as ‘‘a genetically predisposed inflammatory
and pruritic allergic skin disease with characteristic clini-
cal features. It is associated most commonly with IgE
antibodies to environmental allergens’’. Identifying the
pathogenesis of a disease with a ‘‘moving target’’ defini-
tion has been a challenge for veterinarians and physi-
cians alike for many years.
Finding effective, yet safe therapy has also been diffi-
cult. A variety of topical and systemic therapies areavailable, including allergen specific immunotherapy,
glucocorticoids, calcineurin inhibitors, antihistamines
and essential fatty acids. Unfortunately, these therapies
are either not always effective or have adverse side effects
when used long term. The search for the ideal treatment
continues.
In humans with AD there are a number of peripheral
blood abnormalities that may be involved in the patho-genesis of the disease (Boguniewicz et al., 2003; Leung,
1999, 2001; Leung and Bieber, 2003; Sperber Haas,
2002). These include elevated IgE levels, eosinophilia,
increased basophil spontaneous histamine release and
changes in adhesion molecules (VCAM-1, ICAM-1).
Other possible causes of AD are an imbalance between
Th1 and Th2 T cells, an abnormality of cyclic nucleotide
regulation or a defect in lipid composition leading to adefective epidermal barrier function (Boguniewicz
et al., 2003; Fartasch and Diepgen, 1992; Imolawa,
2001; Leung, 1999, 2001; Leung and Bieber, 2003; Sper-
ber Haas, 2002; Van Joost et al., 1992).
There are many mediators and modulators of inflam-
mation that may also be involved in AD. These media-
tors and modulators include histamine, eicosanoids
1090-0233/$ - see front matter � 2005 Published by Elsevier Ltd.
doi:10.1016/j.tvjl.2005.02.012
(prostanoids and leukotrienes), cytokines, adhesion
molecules and even the humoral amplification systems(consisting of four serum protein systems – complement,
coagulation, kinin and fibrinolytic). Currently, there are
many studies investigating the possible primary cause of
AD but few are investigating the factors that mediate
the inflammatory response.
In this issue of The Veterinary Journal, Rory Breathn-
ach and his colleagues at University College, Dublin, of-
fer a new approach to the problems of AD (Breathnachet al., 2005). Rather than trying to identify the primary
defect, the authors seek to identify factors that may
mediate or modulate the inflammatory response in
AD. Specifically they looked at leukotriene B4 (LTB4)
production, complement C3 to C3b conversion and acid
hydrolase enzyme concentrations in peripheral blood
mononuclear cells (PBMCs) and polymorphonuclear
neutrophils (PMNs) from 31 dogs with atopic dermatitis(AD). They found that dogs with AD exhibited a signif-
icant increase in intracellular acid hydrolase enzymes
(b-galactosidase and b-glucuronidase) in both the leuko-
cyte sub-populations and only in PBMC respectively
suggesting that therapy directed toward inhibition of
these enzymes might be helpful in the treatment of AD.
More exciting was the finding of an increase in
LTB4 concentrations within the PMN cells. Since 5-lipoxygenase and leukotriene A4 hydrolase are
responsible for the production of this leukotriene, if
either or both of these enzymes could be blocked,
perhaps symptoms associated with AD may be damp-
ened or inhibited. The availability of 5-lipoxygenase
inhibitors makes this possibility a reality. In one
study with humans these inhibitors were shown to
have benefits to the patients (Woodmansee and Si-mon, 1999). However, in a small study of dogs with
AD the results were disappointing (Crow et al., 2001)
as although erythema was significantly improved in
dogs receiving a 5-lipoxygenase inhibitor, more
importantly, the pruritus did not improve. Since the
pathophysiology of pruritus and inflammation are
not necessarily synonymous, the authors speculated
Guest editorial / The Veterinary Journal 171 (2006) 16–17 17
that it might be that leukotrienes are only involved in
inflammation and not pruritus. A subsequent study
contradicts this result (Senter et al., 2002) in which
the pruritus was effectively reduced by at least 50%
in 2/18 (11%) dogs. More studies need to be done
to clarify this issue.Excessive reactive oxygen species (ROS) production
has been reported in a wide variety of diseases in
man. The data generated in the report by (Breathnach
et al., 2005) reveals large differences in individual
chemiluminescence values for both cell fractions in
dogs with AD. If this significant increase in ROS in
dogs with AD is reproducible, therapy with oxygen
scavengers (e.g., ascorbate, vitamin E, n-acetylcysteineand s-adenosylmethionine) may be of value in dogs
with AD.
An unexplained finding in the study was that in dogs
with AD the mean percentage conversion of C3 to C3b
was significantly higher in AD dogs than normal dogs
while in humans with AD it was lower than unaffected
humans. If this finding were reproducible its possible
involvement in the pathogenesis of AD would be aninteresting area of future studies.
Until we find and correct the underlying defect of AD
it appears that we will continue to attack the disease on
multiple ‘‘fronts’’. The Dublin paper is a good step in
that direction.
Paul Bloom
Allergy and Dermatology Clinic for Animals
31205 Five Mile Road
Livonia, MI 48154, USA
E-mail address: [email protected]
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