Eosinophilic granuloma complex in cats and dogs - VCA Specialty ...

EOSINOPHILIC GRANULOMA COMPLEX IN CATS AND DOGS
The eosinophilic granuloma complex (EGC) in the cat actually consists of three similar
diseases. Despite the name, the three diseases do not always cause granulomas. The
presence of eosinophilic degranulation products have been documented coating but not
altering the collagen in all of these diseases. 1
These diseases are best thought of as inflammatory reactions of the skin, often associated
with hypersensitivity diseases. Thus, the veterinarian should attempt to search for any
underlying diseases. [One article 2 suggest that even Felis domesticus allergen I (Feld I)
could be an autoallergen responsible for chronic inflammatory reactions in cats with
EGC.] Cat skin may respond with eosinophils to as diverse a group of diseases as
allergies, pemphigus, neoplasia, or pyoderma. Thus specific histological as well as
clinical guidelines must be used to make the diagnosis of EGC.
The lip ulcer (eosinophilic ulcer, indolent ulcer, rodent ulcer) is found on the upper lip of
cats. Diagnosis is based on clinical appearance as well as histopathology, which generally
reveals hyperplastic ulcerative superficial perivascular dermatitis with eosinophils or
neutrophils, mononuclear cells and fibrosis. Blood eosinophilia and tissue eosinophilia
are less common than the other diseases in this complex. The major underlying diseases
identified with the indolent lip ulcer are flea allergy 3 , food allergy and atopic dermatitis;
when these are controlled, the lip lesion resolves. Occasionally infection with
Microsporum canis may be responsible for lip ulcers. 4
The eosinophilic plaque is usually seen on the ventral abdomen or inner thigh. Typical
lesions show raised erythematous orange to yellow plaques. Differential diagnosis must
include both granulomatous diseases and neoplasia. Biopsy reveals hyperplastic,
superficial and deep perivascular dermatitis with eosinophilia and at times a diffuse,
eosinophilic dermatitis. Eosinophilic microvesicles and microabscesses may be seen in
the epidermis. The eosinophilic plaque has been associated with the underlying diseases
of food allergy, flea allergy and atopic dermatitis.
Feline eosinophilic granuloma occurs most commonly in the oral cavity or in a linear
fashion on the back legs. A subset of this disease has been associated with mosquito
bites 5 and presents as nodules, with or without ulceration, on the face, ears and feet. This
condition has also been seen on/within the chin of cats (feline chin edema; ‘pouty’ cat)
and affecting the foot pads. Typically, the lesions have a papular to nodular
configuration and histologically show granulomatous dermatitis with multifocal areas of
collagen coated with the released substances from degranulated eosinophils (formerly
known as ‘collagen degeneration’). Eosinophils are common in the biopsies from the face
or oral cavity, and there may be a peripheral eosinophilia as well. Eosinophilic
granuloma of the hind legs has been associated with the underlying disease of flea
allergy; it has also been seen with an apparently genetic predilection in a colony of SPF
(specific pathogen-free) cats. The author has seen cases affecting the foot pads which
were associated with certain types of cat litter.

Definitive diagnosis of the eosinophilic granuloma complex MUST be made on histopathology.
There are simply too many differential diagnoses which may fool the
clinician to make the diagnosis only on visual examination. These would include
neoplasias (lymphoma, mast cell tumor, etc), proliferative, non-neoplastic conditions
(plasma cell pododermatitis) and infections (herpes virus).
Herpes virus dermatitis is probably under-reported. Persistent ulcerative to necrotizing
lesions develop on the face, most typically the nose 6 Affected cats often have a history of
stress, glucocorticoid administration, or chronic ocular or respiratory disease suggesting
this skin disease is associated with reactivation of latent herpes virus infection. However,
the respiratory signs may be subtle, and owners should be questioned carefully to
determine this facet of the history.
Histopathology shows a marked vesicular and ulcerative eosinophilic infiltrate with
intranuclear viral inclusion bodies in the epithelium. Unfortunately, the viral inclusions
are not always readily seen, and the histology can bear some resemblance to idiopathic or
mosquito bite-induced eosinophilic granulomas. Subsequent electron microscopy and
polymerase chain reaction evaluation may confirm the virus to be feline herpes 1.
Treatment:
1) Subcutaneous alpha interferon (Intron A®:Schering; 1 vial contains 3 million units)
has appeared beneficial in some cases, sometimes dramatically so. Dosage is
approximately 1.5-2 million units/m 2 (a 5 kg cat has a m 2 body area of 0.29 meters, and
thus would receive a dose of 290,000-580,000 units) given subcutaneously three times
weekly for at least six weeks. Side effects are uncommon but malaise may be seen. May
be difficult to obtain.
2) Concurrent lysine therapy could be considered: a colleague’s suggested dose is 250 mg
BID for 30 days, then SID to maintain. Use non-propylene glycol containing tablets.
3) Recent anecdotal reports are promising for using topical 5% imiquimod cream
(Aldara®, 3M Pharmaceuticals), a ‘local immunological response modifier’, in the
treatment of feline cutaneous herpes infection. Cats generally only tolerate 2-3 treatments
per week, due to irritation reactions. The drug comes as a dozen 0.25 gm packets. One
packet may supply enough cream for two applications. Cost is around $120 per dozen.
There is an anecdotal report of 2 cats developing reversible leucopenia following
ingesting (via grooming) imiquimod cream which was placed on their lesions.
4) Famcyclovir 40mg/kg tid thus a 5kg cat = ½ of a 500mg tablet tid. Effective – now
available as a generic.
.
Plasmacytic pododermatitis is a rare idiopathic cause of foot pad swelling and ulceration
in cats. The initial condition is a soft, nonpainful swelling of the foot pads, which may
progress to ulceration and granulation tissue. Ulceration may lead to pain and lameness.
Usually the metacarpal or metatarsal pads are involved but the digital pads may also be
affected. Diagnosis is by biopsy, which reveals a diffuse dermatitis with a massive
plasma cell infiltration. 7 This disease may be associated with FIV infection. The best
mode of therapy is still undetermined. Corticosteroids have not always been beneficial. 8

Some cases will regress spontaneously. Doxycycline, 5 mg/kg q 12 h 9 , gold therapy in a
regimen as for plasmacytic-lymphocytic stomatitis 10 or surgical removal of affected
tissues 8 , are treatments that have been reported as effective. Reports from Europe indicate
a high percentage (50%) of these cats are FIV-positive. Researchers using both
immunohistology and PCR were unable to identify any organisms in the lesions. 11
Treatment of feline EGC
Traditionally, these diseases have been treated with intra-muscular injections of
methylprednisolone acetate (Depomedrol®:UpjohnPharmacia) at 4 mg/kg, given once
every two weeks for three injections. The author uses this treatment ONLY IF: the
disease has been confirmed by biopsy, there is no evidence of, or no ability to investigate,
an underlying cause (especially feline herpes virus dermatitis), and this protocol is only
used twice a year at most.
More frequent use of this protocol will lead to the development of diabetes in a very high
percentage of cats. If further corticosteroid treatment is needed, oral prednisolone,
initially at a dosage of 1 mg/kg q12 h may be used, then tapered to the lowest effective
dosage.
In an attempt to avoid corticosteroids, the following treatments have been
reported/utilized:
In one study, 4 of 4 eosinophilic granulomas, but 0 of 2 eosinophilic plaques were shown
to respond to administration of essential fatty acids (DermCaps®:DVM Pharmaceuticals).
Dosages approximated the manufacturer's guidelines. These are welltolerated
medications.
Cyclosporine: a good response to a dose of 25 mg/cat was seen in 6 cases of eosinophilic
plaque and 3 cases of oral eosinophilic granuloma in one report. 12 In three cases of
indolent lip ulcers, the response was less impressive. Another more recent study
confirmed these results with a higher dosage range of 10-12.5 mg/kg. 13
If dermatophytes are present, fluconazole or itraconazole (10 mg/kg q24 h) should be
used – previous anecdotal reports of lip ulcers’ responses to griseofulvin may in fact have
been due to an underlying M. canis infection.
Clavamox has been reported as effective in the treatment of eosinophilic plaques. 13a
Canine Eosinophilic Granuloma Complex
Canine eosinophilic granuloma is most commonly reported in Arctic Circle
breeds and Cavalier King Charles Spaniels, and is most often seen on the inner thighs or
in the mouth 14,15 . Erythematous to yellow raised nodules with papillated surfaces are
typical. Pruritus is variable. Diagnosis is by histology, which is identical to the feline

eosinophilic granuloma, with eosinophils and granulomatous inflammation around
eosinophilic debris-coated collagen. Treatment is with prednisone at 1 mg/kg q12h for
one week, then tapering down over the course of four to six weeks. Occasionally, higher
initial dosages are necessary.
Canine eosinophilic furunculosis is a closely-related disease. It has been
reported in many breeds, but typically is seen in long-nosed large breeds or curious small
breeds (i.e., terriers) with potential access to wasps, bees, ants, spiders, etc. 16 It is thus
felt to be due to arthropod bites or stings. Consistent with this, the disease may be very
rapid in onset, leading to nasal/muzzle swelling, exudation and pain. Large, swollen,
erythematous lesions on the muzzle are the most common lesions, but in some dogs
similar lesions may be seen on the head, periocularly and around the pinna. Impression
smears will often show eosinophils. While diagnosis is usually done on a clinical basis,
histologic confirmation will show lesions similar to that of the canine eosinophilic
granuloma, but with more eosinophilic infiltration into the epidermis and follicular wall,
a furunculosis, and fewer areas of eosinophilic debris-coated collagen. Treatment is as
reported for the canine eosinophilic granuloma.
References
1. Fondati A, Fondevila D, Ferrer L. Histopathological study of feline eosinophilic
dermatoses. Vet Dermatol 2001;12:333-338.
2. Wisselink MA, van Ree R, Willemse T. Evaluation of Felis domesticus allergen I
as a possible autoallergen in cats with eosinophilic granuloma complex. Am J Vet
Res 2002; 63:338-341.
3. Colombini S, Hodgin EC, Foil CS, et al. Induction of feline flea allergy dermatitis
and the incidence and histopathological characteristics of concurrent indolent lip
ulcers. Vet Dermatol 2001; 12:155-161.
4. Moriello KA. Important factors in the pathogenesis of feline dermatophytosis. Vet
Med 2003; 98: 845-858
5. Mason KV, Evans AG. Mosquito bite-caused eosinophilic dermatitis in cats. J Am
Vet Med Assoc 1991;198:2086-2088.
6. Hargis AM, Ginn PE. Feline herpesvirus 1-associated facial and nasal dermatitis
and stomatitis in domestic cats.Vet Clin North Am Small Anim Pract 1999;
29:1281-1290.
7. White SD. Pododermatitis. BSAVA Manual of Small Animal Dermatology, 112-
115, 2003.
8. Guaguère E, Hubert B, Delabre C (1992) Feline pododermatoses. Vet Dermatol 3:
1-12.
9. Bettenay SV, Mueller RS, Dow K, et al. Prospective study of the treatment of
feline plasmacytic pododermatitis with doxycycline. Vet Rec 2003;152:564-566.
10. Medleau L, Kaswan RL, Lorenz MD Ulcerative pododermatitis in a cat:
immunofluorescent findings and response to chrysotherapy. J Am Anim Hosp
Assoc 1982; 18:449- 451.

11. Bettenay SV, Lappin MR, Mueller RS. An immunohistochemical and polymerase
chain reaction evaluation of feline plasmacytic pododermatitis. Vet Pathol
2007;44:80-3.
12. Guaguère E, Prélaud P. Efficacy of cyclosporin in the treatment of 12 cases of
eosinophilic granuloma complex (Abstr). Vet Dermatol 2000; 11 (Supplement 1):
31.
13. Vercelli A, Raviri G, Cornegliani L. The use of oral cyclosporin to treat feline
dermatoses: a retrospective analysis of 23 cases. Vet Dermatol 2006;17:201-206.
13a. Wildermuth BE, Griffin CE, Rosenkrantz WS. Feline pyoderma therapy. Clin
Tech Small Anim Pract. 2006 ;21:150-6.
14. Bredal WP, Gunnes G, Vollset I, et al. Oral eosinophilic granuloma in three
cavalier King Charles spaniels. J Small Anim Pract. 1996;37:499-504.
15. Vercelli A, Cornegliani L, Portigliotti L.Eyelid eosinophilic granuloma in a
Siberian husky. J Small Anim Pract. 2005 ;46:31-33.
16. White SD, Bourdeau P. Hypersensibilité aux dipteres chez les carnivores.
Point Vet 27: 203-6, 1995.

UPDATE ON ATOPIC DERMATITIS AND ITS SECONDARY INFECTIONS
Etiology
Atopic dermatitis is the arguably the second most frequent allergy in dogs (after fleas)
and the third most frequent allergy (after fleas and food) in cats. There is a strong genetic
tendency in dogs, with golden retrievers, Labrador retrievers, terriers, Dalmatians, and
Shar-peis among the predisposed breeds. At the University of California at Davis
(UCD), breeds at greatest risk for atopic dermatitis are Golden Retriever West Highland
White Terrier, Chinese Shar Pei, Bull Terrier, Bichon Frisé, and the Tibetan Terrier. At
Colorado State University (CSU), the three most common groups of breeds examined
with atopic dermatitis are retrievers, terriers and spaniels. In the UK, atopic dogs were
more likely to have atopic offspring- this was particularly evident for atopic sires 1 .
Interestingly, in a large study of West Highland White Terriers, Boxers, and Bullterriers
in Sweden, feeding a diet at least partially home-cooked to the dam was associated with a
lower incidence of atopic dermatitis in the offspring. 2 A genetic tendency has not been
well-documented in cats, but is suspected.
Atopic dermatitis is an allergic response, mediated by IgE. The allergens gain entrance to
the body by either the respiratory or percutaneous route, binding to antibodies in the skin
which are themselves bound to mast cells. This antibody-allergen binding causes the
mast cells to release various inflammatory substances (histamine, etc.). Sensitization is
probably an interaction of the Langerhans’ cells in the epidermis, which bind the antigen
and travel to the regional lymph nodes, and both T and B lymphocytes. It would seem
likely that, as in people and mice, the subclass TH-2 is responsible for promoting B lymphocyte
overproduction of antibody when the Langerhans’ cell presents the antigen. It
has been recently shown that CD4+ T cells ("helper cells") predominate in the skin of
atopic dogs (as they do in people) over CD8+ T cells ("suppressor cells") although both
populations are increased in atopic dogs' skin compared to that of healthy dogs. In a
recent article, atopic dogs were shown to have much higher serum values of IgG1 than
other dogs 3 .
The barrier function of the epidermis is defective in atopic dogs. A recent article
demonstrated that atopic dogs have abnormal (inadequate) lipid interstitium in the
stratum corneum 3a , and unpublished work suggests that some atopic dogs may have a
defect in filaggrin, an important component of the stratum corneum (the outer most,
‘horny’ layer of the epidermis); this may translate into more susceptibility to both
allergen and infective organism access to the skin.
Clinical Presentation
Atopic dermatitis may be seasonal or year round. Dogs most commonly start showing
signs between one to seven years of age. In a recently completed study at UCD, the
average age of affected dogs was 1.66 years, with 95 % of the dogs first showing clinical
signs some time less than 5 years of age 4 . "Exotic breeds", such as the Akita, Shar-Pei
and Chow Chow, may show signs as young as six months. Initially, the season may be
quite short, but as (presumably) the dog becomes allergic to more allergens, year-round

pruritus frequently results. Lesions in dogs are generally found on the feet, ears, axilla,
and face, with conjunctivitis present more frequently than is commonly reported.
Pruritus, typified by erythema, alopecia and hyperpigmentation is the most frequent sign.
Clinical signs may become generalized in severe cases.
In cats, lesions are generally found on the face, rarely on the feet, and occasionally
generalized. Pruritus, typified by erythema, alopecia and hyperpigmentation is the most
frequent sign. Miliary dermatitis and the eosinophilic granuloma complex have also been
reported as being secondary to atopic dermatitis in some cases. Age of onset, breed or
sex predilections have not been well defined in cats.
Atopic dogs are prone to secondary infections with Staphylococcus pseudintermedius
and Malassezia pachydermatis 5, 5a . Thus, clinical signs of superficial pyoderma
(epidermal collarettes, papules), or yeast infection (waxy brown exudate on skin or
proximal claws, erythema interdigitally or under tail) are common. S pseudintermedius
may further exacerbate the atopic state by eliciting production of IgE specific for
Staphylococcus, as well as by producing staphylococcal protein A (SPA), which may
nonspecifically bind to IgE molecules on mast cells. In return, the atopic state may
contribute to or enhance pyoderma, by the pruritus physically reducing the barrier the
stratum corneum poses for infection, by the increased ability of S pseudintermedius to
"stick" to atopic dogs' corneocytes 5b , or by the degranulation of mast cells making the
epidermis more permeable to staphylococcal antigens. In addition, atopic dogs’ carriage
of S pseudintermedius is greater than healthy dogs. 5c While S pseudintermedius is the
most commonly isolated bacteria from superficial pyodermas in dogs, S aureus and S
schleiferi have also been isolated. 6,7 Diagnosis of superficial pyoderma is usually made
by clinical signs; diagnosis of Malassezia infections is made by scrape or tape
preparations of the superficial skin, stained with DiffQwik and examined under oil
immersion. Atopic cats may be prone to secondary infections with S pseudintermedius
and Malassezia pachydermatis, although seemingly not at the same rate as dogs. 6a
It is vital to treat secondary bacterial infections (usually superficial pyodermas), as in
most animals these are also contributing to pruritus. The author uses the following
antibiotics:
Cephalexin 20-30 mg/kg q 8-12 h
Cefpodoxime (Simplicef) 5-10 mg/kg q 24 h
Lincomycin (Lincocin ®) 20 mg/kg q 12 h
Ciprofloxacin 30 mg/kg q24h
Enrofloxacin (Baytril®) 5 - 10 mg/kg q 24 h
Amoxicillin-Clavulanate (Clavamox®) 13.75 mg/kg q 12 h
Marbofloxacin (Zeniquin®) 3- 6 mg/kg q 24 h
Azithromycin 10mg/kg, q24h, 4 days/week
Doxycycline 5mg/kg q12h
TMS 30 mg/kg q12h
Clindamycin 11mg/kg q12 h

With the increase in methicillin-resistant S pseudintermedius, S aureus, and S schleiferi,
the author now strongly recommends culture of any dog with epidermal collarettes that
fails to begin to respond to one of the above antibiotics over a 3-4 week period of time.
Epidermal collarettes may be cultured using a dry sterile culturette rolled across the
collarettes. 8
Shampoos may be helpful as adjunct treatment in pyodermas, particularly in superficial
pyodermas. There are many good, effective anti-bacterial shampoos available. The
author’s favorite is an ethyl-lactate containing shampoo (Etiderm®, Virbac), which is
effective, lathers well, and well-liked by owners. A 4% chlorhexidine – tris-EDTA
shampoo has also shown good results (Triz-chlor 4®, DermaPet).
For treatment of Malassezia, ketoconazole (5mg/kg q24h), itraconazole (5mg/kg q24h) or
fluconazole (5 mg/kg q24h) have all been effective in the author’s hands. Terbinafine (30
mg/kg q24h) may be used in dogs that do not tolerate azoles. Topicals such as Malaseb®
(DVM: chlorhexidine and miconazole), Mal-A-Ket® (Dermapet: boric and acetic acids,
and ketoconazole) or Resizole® (Virbac: miconazole), are helpful. ‘Wipes’; such as
Malaseb®, Malacetic®, or Duoxo® pads are very useful in the treatment of interdigital
yeast and bacteria infections.
Diagnosis
Atopic dermatitis is diagnosed by history, physical examination, and (except in the
"classic" case of recurrent, strictly seasonal "typical" clinical signs, erythema/pruritus of
face, etc.) ruling out other causes of pruritius, especially food allergy, ectoparasites, etc.
Atopic dermatitis is then definitively diagnosed by intradermal skin testing or serologic
tests, looking for allergen-specific IgE. Because of the high incidence of "false positive"
(or, at least, clinically nonsignificant) findings, these tests should only be performed if
other diagnoses have been ruled out.
There is a great deal of controversy over which is the more accurate, intradermal skin
testing or serologic tests. In three studies, at UCD 9 , CSU 10 , and Gifu University (Japan) 11
involving a combination of over 250 dogs, the number of positive responses to
hyposensitization were similar regardless of whether the hyposensitization solutions were
based on IDST results or ELISA tests.
Treatment
The most appropriate treatment is usually hyposensitization injections, which are
effective in about which are effective in about 65% of the dogs treated at UCD, and 70-
80% of the cats in the author’s experience. Hyposensitization requires a tremendous
amount of clinician-client communication, especially so that the owner knows:
1. Hyposensitization should be continued for at least 1 year before final evaluation
of efficacy.
2. If effective, the treatment will almost certainly need to be continued for the
animals life (in our study at UCD, only 2 dogs out of over 150 had their
hyposensitization discontinued without a recurrence in the following 2 years).

3. If effective, the animal may still need ancillary treatment (antibiotics,
antihistamines, fatty acids, etc).
4. Minor side effects (pain at the site of injection) and major side effects
(anaphylaxis—very rare).
5. Expense (in the USA): between $500-$1000 per year, depending upon frequency
of injections (most dogs receive a maintenance injection q7-10 days) and need for
a veterinary examination due to pruritus or minor side effects.
There is some evidence that mold allergens should not be mixed in the same solution as
pollens, possibly because the molds have proteases that degrade the antigenicity of the
pollen proteins 12 . A recent article confirmed early research that allergen solutions for
hyposensitization must be customized to the individual dog (ie, one can not just use a
‘regional mix’}. 12a
If hyposensitization fails or if the owner declines this therapy, antipruritic drugs may be
necessary. Prednisolone (1 mg/kg once daily [double for cats], then tapered to the lowest
every other day dosage needed) is usually effective. Triamcinolone (3-4 mg/cat) or
dexamethasone (0.1 mg/kg daily) then taper; these medicaitons may be used with caution
in cats, but are very ‘Cushing-ogenic’ in dogs.
Antihistamines commonly used in dogs are diphenhydramine (2.2 mg/kg t.i.d.),
hydroxyzine pamoate (2.2 mg/kg t.i.d.), chlorpheniramine (0.2-0.8 mg/kg b.i.d. to t.i.d.),
or clemastine (0.1 mg/kg b.i.d.); in one study 13 diphenhydramine and hydroxyzine were
both the most commonly used antihistamines and the most frequently effective. In cats,
chlorpheniramine (2-4 mg/5 kg b.i.d.) or clemastine (0.1 mg/kg b.i.d.) may be used.
Tricyclic antidepressants are sometimes helpful in controlling pruritus. In dogs, those
used are amitriptyline (2.2 mg/kg b.i.d.), or doxepin (2.2 mg/kg b.i.d.). In cats, the author
has used amitriptyline (5-10 mg/cat b.i.d.).
A combination medication of trimeprazine 5mg and prednisone 2 mg (Temeril-P®
[Vanectyl-P® in Canada], Pfizer) has been quite helpful in reducing the amount of
prednisone which must be given to atopic dogs. The drug is given at an empiric dose of 1
tablet b.i.d. for dogs less 10 kg, 2 tablets b.i.d. for dogs between 10 and 25 kg, and 3 tablets
b.i.d. for dogs over 25 kg.
Products containing essential fatty acids (EFA) have been used as nonsteroidal
antipruritics. These drugs apparently interfere with the production and metabolization of
arachidonic acid and other "pro-inflammatory" substances. The author has not
distinguished a difference in efficacy between EFA supplements of omega 3 fatty acids
and those containing a mixture of omega 3 and 6. In dogs, these may have as high as 25%
chance of reducing pruritus, particularly when combined with antihistamine treatment.
When EFA supplements are included in the dog food, the success rate in one open trial
was 42% (good to excellent control of pruritus) 14 ; in another trial it was 44%. 15 In this
latter trial, dogs responding to the test diet had a different pattern of fatty acid change in
the plasma and the skin as compared to the dogs which failed to respond to the diet,

suggesting that there are subsets of atopic dogs with different fatty acid metabolism
capabilities. Somewhat in contrast, a recent article noted that the improvement seen in
atopic dogs with EFA supplementation did not seem to be correlated with total fatty acid
intake or with the ratio of omega 6:3 fatty acids. 16 A very well written report documented
the steroid-sparing effect of EFAs in some atopic dogs. 17 Another report documented
some beneficial effect in the use of dog foods enriched with EFAs, 17a , while a recent
report documented improvement in puritus when atopic dogs were fed certain diets that
were recommended for allergic dogs. 17b
Antihistamines in conjunction with essential fatty acids may give relief from clinical
signs in as high as 50% of atopic cats.
Cyclosporine is available as Atopica® (Novartis) in 10, 25, 50 and 100 mg capsule sizes.
Ideally, this should be given on an empty stomach, but if this causes GI upset,
administration with food may help. It is well-tolerated in most dogs. Because low doses
are used for treating atopic dermatitis, usually 5-7 mg/kg/day or less, adverse effects are
uncommon. 18 The most common problem is nausea and loss of appetite. Because of
expense, particularly in large breed dogs, administration concurrently of ketaconazole
will enable a reduction of Atopica® dosage. (This is due to the body’s metabolism of
both drugs). 19 In general, with a dose of ketoconazole of 5mg/kg, the author has seen
good results using only 50% of the canine dose of cyclosporine (2.5 mg/kg per day
instead of 5mg/kg per day). A recent article suggests that as many as >35% of atopic
dogs treated with cyclosporine for 4 months may not relapse for as long as 40 days after
cessation of the cyclosporine. 20
Oatmeal-based shampoos, or shampoos containing 0.5-1.0% hydrocortisone, are also
helpful adjunctive therapies in the dog (or rare cat that enjoys a bath). Ideally, they
should be used at least two to three times per week. The introduction of "Resi" products,
basically rinses designed to be left on the pet, have given encouraging results. Chief
among these is Resi-Cort (Virbac) a 1% hydrocortisone product, which may be used
once to twice weekly.
A few new topical products that may be helpful in bathing atopic dogs are:
Genesis Spray (VIRBAC). The active ingredient is 0.015 % triamcinolone acetonide.
While not optimal for long term management, this spray has a low risk of corticosteroid
side-effects if used on problem areas (especially the feet) to ‘cool down’ the pruritic
response.
Allermyl Shampoo and Spray (VIRBAC). These contain linoleic acid as a potential
anti-pruritic, as well as the anti-infectives piroctone olamine and monosaccharides.
Duoxocalm ® shampoo, spot-on and spray (Sogeval). Recently released in the USA, these
products contain sphingophytosine, a substance that may normalize the stratum corneum
in atopic dogs, as well as hinokitol, a plant derived substance with anti-infective
properties. It is now the widest used non-steroid anti-pruritic shampoo in France,
according to the company. The Duoxocalm ® Seborrhea Spot-on may also be effective in
this regard.
Allerderm Spot-On ® (VIRBAC) contains ceramides and may normalize the stratum
corneum in atopic dogs/

Tacrolimus ointment [Protopic: Fujisawa] has been shown to be safe and effective for the
treatment of moderate to severe atopic dermatitis in humans. The 0.1% concentration is
recommended for adults and the 0.03 % for treatment in both children and adults for
long-term intermittent therapy in patients not adequately responsive to, or intolerant of,
conventional therapy. The efficacy of the 0.1% product has recently been reported in
dogs. 21 This is a semi-expensive product (30 gm tube = $70-120).
References
1. Shaw SC, Wood JL, Freeman J, et al. Estimation of heritability of atopic
dermatitis in Labrador and Golden Retrievers. Am J Vet Res. 2004 Jul;65:1014-
1020.
2. Nedtvedt A, Bergvall K, Sallander M, et al. A case-controlled study of risk factors
for canine atopic dermatitis among boxer, bullterrier and West Highland white
terrier dogs in Sweden. Veterinary Dermatology 2007; 18:309-315.
3. Fraser MA, McNeil PE, Gettinby G. Examination of serum total IgG1
concentration in atopic and non-atopic dogs. J Small Anim Pract 2004;45:186-
190.
3a. Piekutowska A, Pin D, Rème CA, et al. Effects of a topically applied preparation
of epidermal lipids on the stratum corneum barrier of atopic dogs. J Comp Path
2008; 138:197-203.
4. Zur G, Ihrke PJ, White SD, Kass PH. Canine atopic dermatitis - a retrospective
study of 266 cases seen at the University of California at Davis, 1992-1998. Part I
- Clinical features, and allergy test results. Vet Dermatol 2002; 13: 89-102.
5. White SD, Bourdeau P, Blumstein P, et al. Comparison via cytology and culture
of carriage of Malassezia pachydermatis in atopic and healthy dogs. In: Kwochka
KW, Willemse T, von Tscharner C, eds. Advances in Veterinary Dermatology,
Vol. 3. Oxford: Butterworth Heinemann, 1998; 292-298.
5a. Griffin CE, DeBoer DJ. The ACVD task force on canine atopic dermatitis (XIV):
clinical manifestations of canine atopic dermatitis. Veterinary Immunology and
Immunopathology 2001; 81: 255–69.
5b. McEwan NA, Mellor D, Kalna G. Adherence by Staphylococcus intermedius to
canine corneocytes: a preliminary study comparing noninflamed and inflamed
atopic canine skin. Veterinary Dermatology 2006; 17: 151–4.
5c. Fazakerley J, Nuttall T, Sales D, et al. Staphylococcal colonization of mucosal
and lesional skin sites in atopic and healthy dogs. Vet Dermatol 2009;20:179-84.
6. Frank LA, Kania SA, Hnilica KA, Wilkes RP, Bemis DA. Isolation of
Staphylococcus schleiferi from dogs with pyoderma. J Am Vet Med Assoc 2003;
222:451-454.
6a. Ordeix L, Galeotti F, Scarampella F, et al. Malassezia spp. overgrowth in allergic
cats. Vet Dermatol 2007;18:316-323.
7. Morris DO, Rook KA, Shofer FS, et al. Screening of Staphylococcus aureus,
Staphylococcus intermedius, and Staphylococcus schleiferi isolates obtained from
small companion animals for antimicrobial resistance: a retrospective review of
749 isolates (2003-04). Vet Dermatol 2006;17:332-337.

8. White SD, Brown A, Chapman P, et al. Aerobic bacterial culture of epidermal
collarettes in dogs. J Am Vet Med Assoc, 2005; 226:904-908.
9. Zur G, White SD, Ihrke PJ, Kass PH, Toebe N. Canine atopic dermatitis - a
retrospective study of 169 cases seen at the University of California at Davis,
1992-1998. Part II - Response to Hyposensitization. Vet Dermatol 2002; 13: 103-
11.
10. Scott KV, White SD, Rosychuk RAW. A retrospective study of hyposensitization
in atopic dogs in a flea-scarce environment. In: Ihrke PJ, Mason I, White SD, eds.
Advances in Veterinary Dermatology Vol 2. Oxford: Pergamon Press, 1993; 79-
87.
11. Park S, Ohya F, Yamashita K, Nishifuji K, Iwasaki T. Comparison of response to
immunotherapy by intradermal skin test and antigen-specific IgE in canine atopy.
J Vet Med Sci. 2000 62: 983-8.
12. Schnabl B, Bettenay SV, Dow K, Mueller RS. Results of allergen-specific
immunotherapy in 117 dogs with atopic dermatitis.Vet Rec. 2006 ;158:81-85.
12a. Willemse T, Bardagi M, Carlotti DN, et al. Dermatophagoides farinae-specific
immunotherapy in atopic dogs with hypersensitivity to multiple allergens: A
randomised, double blind, placebo-controlled study. Vet J. 180: 337–342, 2009.
13. Zur G, Ihrke PJ, White SD, Kass PH. Antihistamines in the management of
canine atopic dermatitis: A retrospective study of 171 dogs (1992-1998).
Vet Therapeut 3:1:88-96, 2002.
14. Rosychuk RAW, Scott-Fieseler K, White SD, Shackleford S.: Nutritional
management of canine atopy in 47 dogs: a retrospective study. In Reinhart GA,
Carey DP, eds. Recent Advances in Canine and Feline Nutritional Research
Volume III: 2000 Iams International Nutrition Symposium Proceedings.
Wilmington: Orange Frazer Press, 2000; 287-91.
15. Scott DW, Miller WH Jr, Reinhart GA, Mohammed HO, Bagladi MS. Effect of
an omega 3/omega-6 fatty acid-containing commercial lamb and rice diet on
pruritus in atopic dogs: results of a single-blinded study. Can J Vet Res 1997;
61:145-53.
16. Mueller RS, Fieseler KV, Fettman MJ, et al. Effect of omega-3 fatty acids on
canine atopic dermatitis. J Sm Anim Pract 2004 Jun;45:293-297.
17. Saevik BK, Bergvall K, Holm BR et al. A randomized controlled study to
evaluate the steroid sparing effect of essential fatty acid supplementation in the
treatment of canine atopic dermatitis. Vet Dermatol 2004 15:137-145.
17a. Bensignor E, Morgan DM, Nuttall T. Efficacy of an essential fatty acid-enriched
diet in managing canine atopic dermatitis: a randomized, single-blinded, crossover
study.Vet Dermatol. 2008;19:156-162.
17b. Glos K, Linek M, Loewenstein C, Mayer U, Mueller RS. The efficacy of
commercially available veterinary diets recommended for dogs with atopic
dermatitis. Vet Dermatol 2008 19:280-287.
18. Olivry T, Steffan J, Fisch RD, et al. Randomized controlled trial of the efficacy of
cyclosporine in the treatment of atopic dermatitis in dogs. J Am Vet Med Assoc
2002; 221: 370-7.

19. Steffan J, Horn J, Gruet P, et al. Remission of the clinical signs of atopic
dermatitis in dogs after cessation of treatment with cyclosporin A or
methylprednisolone. Vet Rec 2004;154:681-684.
20. Patricelli AJ, Hardie RJ, McAnulty JE. Cyclosporine and ketoconazole for the
treatment of perianal fistulas in dogs. J Am Vet Med Assoc 2002; 220:1009-1016.
21. Marsella R, Nicklin CF, Saglio S,et al. Investigation on the clinical efficacy and
safety of 0.1% tacrolimus ointment (Protopic) in canine atopic dermatitis: a
randomized, double-blinded, placebo-controlled, cross-over study. Vet Dermatol
2004 ;15:294-303.

UPDATE ON FOOD ALLERGY
Etiology
The exact etiology in most clinical cases is not well understood. Food allergy is defined
as an immunologically based reaction to food. Immunologic mechanisms of types I-IV
have been hypothesized. A recent report measured cell-mediated immunity (via
lymphocyte blastogenesis against food allergens( in both proven food allergic dogs and
healthy dogs. The significantly higher responses of the food allergic dogs to the foods
they were allergic to lends some credence to the role of cell-mediated immunity in this
disease 1 . On the other hand, another recent report found that in 10 dogs allergic to either
beef, cow’s milk, or lamb, all the dogs had specific IgE antibodies against bovine IgG. 2
(There may be some evidence that this reaction could be due to fetal calf serum used in
the vaccines – although this needs to be investigated further). 3 In further contrast, food
intolerance is a general term describing any adverse reaction to food that does not have
an immunologic basis, including food poisoning (caused by the direct action of a toxin).
From a practical basis, the mechanism of action does not impact the clinician faced with a
potential case of chronic food-caused cutaneous disease. It is theorized that most food
allergens are proteins.
Signalment
No sex predilection has been reported for food allergy in dogs or cats. In some studies, no
breed predilection was noted. In contrast, two studies 4,5 found that certain dog breeds
may have a risk for the development of food allergy: Soft-Coated Wheaton Terrier,
Dalmatian, West-Highland White Terrier, Collie, Chinese Shar Pei, Llasa Apsa, Cocker
Spaniel, Springer Spaniel, Miniature Schnauzer, Labrador Retriever Dachshund and the
Boxer. Breed data from Colorado State University shows that retrievers may be at greater
risk to develop food allergy than other breeds of dogs.
While the age at presentation has been reported as variable, several researchers now feel
that at least 33% of their cases in dogs are of animals less than 1 year of age 4 . Clearly,
while food allergy may occur at any time in animal’s life, it should always be considered
as a differential of pruritus in the young dog.
History and Clinical Signs
The most common clinical sign of food allergy is non-seasonal pruritus which is usually
generalized 6,7 . Pruritus may also be primarily directed at the feet or ears. Very rarely,
food allergic dogs with skin lesions but without pruritus have been reported. 6 The most
common primary dermatologic lesions are papules and erythema; common secondary
lesions are epidermal collarettes (usually indicating a pyoderma) pyotraumatic dermatitis
(‘hot spots’) hyperpigmentation, and seborrhea. Clinical signs of food allergy have been
reported in Cocker Spaniels identical to the idiopathic seborrhea associated with that
breed. Food allergy as the underlying cause of idiopathic onychodystrophy (misshapen,
splitting claws [nails]) has been reported in 2 dogs. 8

Food allergy in cats may present as pruritus of the head and face, milliary dermatitis, or
one of the manifestations of the eosinophilic granuloma complex. 9,10
Reported concurrent gastrointestinal (GI) signs among dogs with cutaneous signs of food
allergy are rare; it is unknown if this is due to a true dearth of GI signs or if in fact
changes in the stool of these dogs were relatively subtle and/or were not noted or
volunteered by the owners while obtaining the history. However, a recent report
documented 20 dogs with both pruritus and GI signs typical of colitis: fecal mucus, fecal
blood, tenesmus and increased fecal frequency. 11 Both cutaneous and GI signs resolved
upon feeding the dogs an elimination diet. Lymphocytic-plasmacytic colitis has been
linked to food allergy in cats and cheetahs. 9 In one study, having both GI and skin signs
increased the likelihood of a diagnosis of food allergy, in a small number of cats. 12
Neurologic signs such as malaise and seizures rarely have been reported. The author feels
that malaise may be under-reported, as an increase in energy level (‘acting like a puppy,
feeling better’) is often noted upon feeding the dog a diet without the offending allergen;
this may occur before cessation of pruritus. Respiratory signs such as asthma have also
been reported, but seem to be quite rare.
Concurrent hypersensitivities have been reported in dogs, and include atopic dermatitis,
flea allergy dermatitis, intestinal parasite allergy and even an allergy to bovine insulin. 6 A
dog has been reported with a cross reaction between exposure to pollen of Japanese cedar
and ingestion of tomatoes. 13 Concurrent pyoderma and/or Malassezia pachydermatis
infection is also common. Dogs may have pyoderma (superficial or deep) as the only
clinical sign of food allergy: These dogs are often clinically normal (i.e., non-pruritic)
while receiving antibiotics. Therefore it becomes quite important to diagnose and treat
secondary infections, as persistence of pruritus due to these infections may confound the
ability of the clinician to diagnose the underlying allergy.
Diagnostics
The ideal method of diagnosis is the feeding of an elimination (“hypoallergenic”) diet
7, 9, 10, 14
. The experience of the author and of other researchers has been disappointing in
the use of serologic or intradermal skin tests to diagnose food allergy in pets in North
America.
The elimination diet ideally contains one protein and one starch. These must be based on
previous exposure of the dog to various food stuffs. Important to remember is that dogs
who live in households with cats tend to have been exposed to fish, through their
consumption of either cat food or cat feces. At UC Davis we often start dogs with pork
and potatoes, although pinto beans and potatoes may also be used. Based on nonexposure,
rabbit, duck, and tuna are also options. We have also used ‘exotic’ foods like
elk when feasible. Other than fresh water, nothing else should be fed to the dog during
the elimination diet trial. This means that vitamins and chewing toys must be eliminated,
and that flavored medications (such as certain ecto/endoparasite preventatives) should be
replaced by other, equally effective non-flavored preparations. Protein-flavored
toothpaste should be replaced by the malt-flavored variety. Because the elimination diet
4, 6,

is not a balanced one, owners should be warned that the dog may lose weight, develop a
‘dull’ haircoat or scaling, or be hungrier than usual. In cats, we often use pork and tapioca
(the latter made with water rather than milk).
Because many owners are unable or unwilling to cook for their pet for the time period
needed, the dermatology service at UC Davis uses commercially available limitedantigen
diets. For dogs these would include Purina LA (salmonid); Iams FP (fish and
potato) and KO (kangaroo and oats); IVD (now owned by Royal Canin) duck, venison,
whitefish, or rabbit plus potato; Hills D/D (duck or fish and rice); or Waltham fish and
rice (also now owned by Royal Canin). For cats these would include IVD duck, venison,
or rabbit plus potato; Hills D/D feline; or Iams lamb and barley. Another option for
animals who already have been fed many foods, or whose dietary history is unknown, is
the use of hydrolyzed protein diets, in which the protein source is hydrolyzed to small
molecular weights, thus avoiding the body’s ‘immunologic radar’. Such foods for dogs
include Purina HA (hydrolyzed soy) , Hills Z/D, or DVM Exclude; for cats the author has
used Hills feline Z/D, or Purina HA for cats. Usage of a commercially prepared diet will
give an approximately 90% chance of determining a food allergy; however, none of these
diets will work for all animals, and failure of an animal to improve on such a diet may
warrant trying another one, or a home-cooked diet in another trial.
The length of the elimination diet is somewhat controversial, however, our observations
have justified a dietary trial of 8 to 12 weeks. Persistence of some pruritus at 12 weeks
into the diet trial may indicate the need for continuing the diet, but may also indicate the
presence of concurrent hypersensitivities. In cases where antibiotics are given to treat
secondary infections, or oral corticosteroids for severe pruritus, the diet must be
continued for a minimum of 2 weeks past discontinuation of these treatments, in order to
properly judge its efficacy.
Upon resolution of clinical signs with the feeding of an elimination diet, the animal
should be challenged with its regular diet to confirm the diagnosis of a food allergy.
Recurrence of clinical signs is usually noted within two week 15 . At that point the animal
is given its elimination diet again, and the owner may then elect to challenge with
suspected allergens, each allergen being given one to two weeks at a time. The most
common proven allergens in the dog are beef, chicken, milk, eggs, corn, wheat, and soy
14 ; in the cat, fish, beef, milk and milk products. 9 Allergies to more than 2 allergens are
uncommon. Once the offending allergens are identified, commercially prepared dog
foods that do not contain them may be fed to the dog. In cases in which the owners
refuse to do provocative testing, one of the limited antigen pet foods may be used as a
maintenance diet.
References
1. Ishida R, Masuda K, Kurata K, Ohno K , et al. Lymphocyte blastogenic responses
to inciting food allergens in dogs with food hypersensitivity. J Vet Intern Med
2004;18: 25-30.

2. Martin A, Sierra MP, Gonzalez JL, et al. Identification of allergens responsible
for canine cutaneous adverse food reactions to lamb, beef and cow's milk. Vet
Dermatol 2004;15:349-356.
3. Ohmori K, Masuda K, Maeda S,et al. IgE reactivity to vaccine components in
dogs that developed immediate-type allergic reactions after vaccination. Vet
Immunol Immunopathol. 2005;104:249-256
4. Rosser EJ: Diagnosis of food allergy in dogs. J Am Vet Med Assoc 203:259-62,
1993.
5. Denis S, Paradis M.: L’allergie alimentaire chez le chien et le chat. 2. Étude
rétrospective. Med Vét Québec 24:15-20, 1994.
6. White SD: Food hypersensitivity in the dog: 30 cases. J Am Vet Med Assoc
188:695-8, 1986.
7. Carlotti DN, Remy I, Prost C: Food allergy in dogs and cats: A review and report
of 43 cases. Vet Dermatol 1:55-62, 1990.
8. Mueller RS, Friend S, Shipstone M, et al. "Diagnosis of canine claw disease - A
Prospective Study of 24 Dogs". Vet Dermatol 2000; 11: 133-41.
9. White SD, Sequoia D: Food hypersensitivity in cats: 14 cases (1982-1987). J Am
Vet Med Assoc 194:692-5, 1989.
10. Rosser EJ: Food allergy in the cat: a prospective study of 13 cats. In: Ihrke PJ,
Mason I, White SD, eds. Advances in Veterinary Dermatology Vol 2. Oxford:
Pergamon Press, 1993; 33-9.
11. Paterson S: Food hypersensitivity in 20 dogs with skin and gastrointestinal signs.
J Sm Anim Pract 36:529-534, 1995.
12. Guillford WG, Markwell PJ, Jones BR, et al. Prevalence and causes of food
sensitivity in cats with chronic pruritus, vomiting or diarrhea. J Nutrition
1998;128(12 Suppl):2790S-2791S.
13. Fujimura M, Ohmori K, Masuda K, et al. Oral allergy syndrome induced by
tomato in a dog with Japanese cedar (Cryptomeria japonica) pollinosis. J Vet Med
Sci 2002;64:1069-70.
14. Jeffers JG, Meyer EK, Sosis EJ. Responses of dogs with food allergies to singleingredient
dietary provocation. J Am Vet Med Assoc 1996; 209: 608-11.
15. Harvey RC: Food allergy and dietary intolerance in dogs: a report of 25 cases. J
Sm Anim Pract 34:175-179, 1993.

FLEA CONTROL
Note: the opinions expressed below are those of Stephen D. White, DVM, DACVD, who
is solely responsible for any errors or omissions.
The flea still causes flea allergy (FAD) in our small animals, and must always be
considered the most likely cause of tailhead/inguinal pruritus in the dog, and
tailhead/inguinal/caudal neck pruritus in the cat (as well as a possible cause of
eosinophilic lip ulcer). However, there is no doubt that with the proliferation of effective
and safe flea control drugs over the last 25+ years, veterinarians have a better chance in
controlling these accursed insects and giving a measure of relief to our patients.
The key point to remember is consistency – owners who only treat their animals once in a
while, only when they see the dog or cat scratch, or only the affected animal (and not the
in-contact pets) will become disappointed and frustrated. The treatments must be tailored
to the animal’s environment, the degree of pruritus, how many other pets are present, and
how much the owners want to spend. In theory, pets should be treated with both an
adulticide and a growth regulator – thus killing the biting adults as well as preventing
their replacement – remember that at any one time, there are probably 10 times as many
immature stages (eggs, larvae, pupae) in the environment as there are adult fleas on the
pet. Also, despite their claims, all the topical spot-on do poorly when an animals has
frequent baths or swims a lot (the oral products are indicated in these dogs). In addition,
these topical spot-ons work much better for most very flea-allergic animals if
administered every 3 weeks instead of every 4 weeks. Finally, almost all the topical
products have occasionally been associated with adverse topical reactions of alopecia,
erythema, ulcers, etc.
An important point is that the oral medications (Capstar®, Comfortis TM ) work much
faster than the topicals. That is probably why they are able to effect the total flea
population, in spite of only killing the adults.
It is also important to realize that with the exception of the products with permethrin, none
of the flea-control products are repellants, thus the owners may see fleas on their animals
for a day after treatment.
The major medications (listed roughly in the order they became available in the USA):
Lufenuron (Program®; Novartis) is administered once a month at 30 mg/kg for cats,
10/mg/kg for dogs. It is also available as a twice yearly injection for cats. This compound
does not affect the adult flea, but rather causes an interruption in normal chitin production
through different specific modes of action. This causes death of the immature, developmental
life stages of the flea. Thus the control of the adult flea infestation on the animal is
via the elimination of the environmental life stages of the flea. There is a lag phase of six to
eight weeks between the initiation of administration and reduction in the number of adult
fleas on the treated cats. The lag phase results from the survival of immature fleas that
were present in the environment before the onset of treatment. This lag phase can be
reduced by initiating oral treatment in combination with premise and/or on-animal

insecticide treatments. The author does NOT recommend the injectable form due to a
report of its possible association with sarcoma. 1
Imidacloprid (Advantage®; Bayer), a chloronicotinyl nitroguanidine synthesized from the
nitromethylene class of compounds, works by binding to the insect's nicotinyl receptor sites
on the postsynaptic neuron, thus disrupting normal nerve transmission. The nervous system
of the insect becomes impaired and the insect dies. It is not effective against ticks.
Generally a once monthly reapplication rate is recommended, however, in severe cases, q3
weeks may be more effective. Available as a spot-on, this is very well tolerated by pets. It
is even approved for use in rabbits in the UK.
Imidacloprid combined with 44% permethrin (Advantix®; Bayer); it must NOT
be used in cats !! Kills and repels fleas, lice, deer ticks (Ixodes spp), American
dog ticks (Dermacentor variabilis) , brown dog ticks (Rhipicephalus
sanguineus), and lone star ticks (Amblyomma americanum).
Imidacloprid combined with moxidectin (Advantage-Multi® ([Advocate® in
Europe]; Bayer). It is approved for heartworm, ‘French heart worm’, intestinal
parasites, and Otodectes cynotis (in cats). It has been shown to be effective in the
treatment of canine demodicosis when applied weekly, although it is not
approved for this in the USA. 2
Fipronil and methoprene (FrontlinePlus®; Rhône-Mérieux). Fipronil is an
insecticide/acaricide belonging to the phenylpryazole family (fipronil). It has efficacy
against fleas and ticks. Generally a once monthly reapplication rate is recommended, but
for severe FAD, every 3 weeks is better. Approved for dogs and cats. Note: fipronil is
contra-indicated on rabbits and hedgehogs.
Selamectin (Revolution® [in the USA] Stronghold® [in Europe]; Pfizer) is an avermectin
that shows effectiveness in heartworm prevention and activity against adult, larvae, and
egg stages of fleas, ear mites (Otodectes cynotis), Sarcoptes, the American dog tick
(Dermacentor variabilis) and a variety of internal parasites. It has also been shown to be
effective against biting and sucking lice. 3,4 It is absorbed into the body and continually
secreted on to the skin. It is marketed for once monthly topical application. Clinically it is
probably the slowest acting of the spot-ons on dogs; however on cats seems to be more
effective than other spot-ons, especially in stopping blood-feeding by the fleas. 5 It is also
helpful in those animals which are on a limited allergen diet trial and thus can’t have
flavored endo/ectoparasiticides.
Nitenpyram (Capstar ® Novartis) is an oral flea adulticide, a neonicotinoid which
selectively binds and inhibits insect specific nicotinic acetylcholine receptors. It has a
large safety index in mammals and has been developed for use in cats (and dogs) at dose
ranges between 1 and 11.4mg/kg. It comes in two sizes: one for small dogs and cats, and
one for larger dogs. Capstar ® is very rapidly absorbed and reaches effective blood levels
within 15-30 minutes of administration. The resulting observed efficacy is equally rapid
with fleas starting to die and fall from animals from 30 minutes onwards. Laboratory and
field based studies demonstrate 95-100 % efficacy within 6 hours and 100 % at 24 hours.
A large percentage of fleas are found having fallen from the animal within 6 hours.

Excretion of the product is equally rapid with effective blood levels only being
maintained for approximately 24 hours in the dog and 36 hours in the cat. Capstar ®
offers an easily administered, very rapid and complete efficacy with high degrees of
safety and a short duration of activity. As such, it represents a good product for flea
control alongside insect growth regulators. Some animals do well on this drug alone, in
spite of the fact that the fleas must bite the pet in order to die. Very rarely, an animal may
become transiently pruritic, ostensibly due to the dying fleas. Recently it has been
suggested that dosing at q48h is sufficient for the dog, and three times a week for cats.
Metaflumizone and amitraz (ProMeris TM for dogs, Fort Dodge). A topical product.
Metaflumizone is a new insecticide, and works at axon (rather than at synapse) level. It
kills flea adults, reduces egg production, but does not repel adult fleas. Controls ticks for
up to 1 month. Approved as a treatment for canine demodicosis at q2 weeks, probably
works better weekly. 6
Unpleasant smell, and has been associated with pemphigus foliaceus-type drug
reactions in 22 dogs. In 64% of these dogs, the lesions were present distant from the
application site, and in 59% of the cases, immunosuppressive therapy was needed even
upon discontinuing the Promeris TM . 7
Metaflumizone (ProMeris TM for cats, Fort Dodge) like for the product for dogs, but
without the amitraz, the unpleasant smell, or the pemphigus foliaceus-type drug reactions
(and also without the tick or demodex indications).
Spinosad (Comfortis TM , Lilly) Thus far only approved in dogs.
New oral chewable (beef-flavored) tablet, approved for dogs. Activates nicotinic
acetylcholine receptors. Company data supports once monthly administration. Some dogs
may need dosing twice monthly. Adverse effects – occasional vomiting. If vomiting
occurs within an hour of administration, redose with another full dose.
Do NOT used at the same time as extra-label (i.e., q24-48h 0.3-0.6 mg/kg) ivermectin
treatment for demodicosis, due to the occurrence of neurologic signs
(trembling/twitching, salivation /drooling, seizures, incoordination, excessive dilation of
pupils, blindness and disorientation).
Dinotefuran, pyrproxifen and permethrin (Vectra 3D TM , Summit VetPharm) for dogs.
A topical product, new neonicotinoid insecticide (Dinotefuran), based on acetylcholine
structure. Pyriproxifen is an Insect Growth Regulator (IGR), and permethrin is the
repellant. Effective against fleas, ticks, mosquitoes, lice, mites (what kind? Probably only
Cheyletiella) and sand flies (the vectors of Leishmaniosis). Like other permethrin
containing compounds, NOT for use in cats.
Dinotefuran and pyrproxifen (Vectra TM , Summit VetPharm) topical for cats. 8 As for
dogs, but without the permethrin, thus no repellant and no effect on ticks, mosquitoes,
lice, mites or sand flies.

Not yet in the USA:
Pyriprole (Prac-tic®; Novartis). A topical product, approved for use in dogs for the
treatment and prevention of flea infestation (Ctenocephalides canis and C. felis) in dogs.
Insecticidal efficacy duration against new infestations with fleas persists for a minimum
of 4 weeks. Also for the treatment and prevention of tick infestation (Ixodes ricinus,
Rhipicephalus sanguineus, Ixodes scapularis, Dermacentor reticulatus, Dermacentor
variabilis, Amblyomma americanum) in dogs. Available in Europe.
REFERENCES
1. Esplin DG, Bigelow M, McGill LD, Wilson SR: Fibrosarcoma at the site of a
lufenuron injection in a cat. Vet Cancer Soc Newsl 23:8-9, 1999.
2. Paterson TE, Halliwell RE, Fields PJ, et al. Treatment of canine-generalized
demodicosis: a blind, randomized clinical trial comparing the efficacy of Advocate(Bayer
Animal Health) with ivermectin. Vet Dermatol 2009;20:447-55.
3. Gunnarsson L, Christensson D, Palmér E. Clinical efficacy of selamectin in the
treatment of naturally acquired infection of sucking lice (Linognathus setosus) in dogs. J
Am Anim Hosp Assoc 2005;41:388-94.
4. Shanks DJ, Gautier P, McTier TL, et al Efficacy of selamectin against biting lice
on dogs and cats. Vet Rec 2003;152:234-7.
5. McCoy C. Broce AB, Dryden MW. Flea blood feeding patterns in cats treated
with oral nitenpyram and the topical insecticides imidacloprid, fipronil and
selamectin. Vet Parasit 2008; 156: 293-301.
6. Fourie LJ, Kok DJ, du Plessis A,, et al. Efficacy of a novel formulation of
metaflumizone plus amitraz for the treatment of demodectic mange in dogs. Vet Parasitol
2007; 150:268-74.
7. Oberkirchner U, Linder K, Olivry T. Promeris-associated pemphigus foliaceouslike
drug reactions in dogs: 22 cases. Proceedings of the North American Veterinary
Dermatology Forum 2010; 206.
8. Murphy M, Ball CA, Gross S.Comparative in vivo adulticidal activity of a topical
dinotefuran versus an imidacloprid-based formulation against cat fleas (Ctenocephalides
felis) on cats. Vet Ther 2009;10:9-16.

DISEASES THAT CAN FOOL US
PART 1 NUTRITIONALLY-RESPONSIVE DISEASES
Sebaceous Adenitis
Sebaceous adenitis is best classified as a peri-folliculitis. There seem to be two forms of
this disease. In the focal form, there are localized areas of alopecia, erythema, and
excessive scaling. The scale characteristically is very adherent to hairs, and frequently
encircles the hairshaft as it leaves the follicle – ‘follicular casting’. The head and
extremities appear to be more consistently involved. Inflammation and pruritus are
variable but may be present, especially with a superficial pyoderma. This form is more
common in short coated breeds (e.g., viszla), and often starts with head or facial
involvement and progresses caudally.
A generalized form with dramatic amounts of scale on the skin, scale adherent to hairs
and the coat and skin often dry to the touch 1 . As the disease progresses (often caudally
from the face or head), there is a generalized thinning of the coat. The dorsal back,
medial aspect of the pinnae and the ear canals usually are the most affected. Pruritus is
variable but may be marked, especially if a secondary bacterial pyoderma present.
Breeds which are predisposed to this form include the Standard poodle, Samoyed, Akita,
Old English sheepdog, and the Lhasa apso 1,2 .
An inflammatory process is responsible for destroying the sebaceous glands in the
affected areas. The reason for the initiation of the inflammatory problem is unknown at
present. Marked orthokeratotic hyperkeratosis is also noted. This derangement in
keratinization may at least in part be a product of the lack of sebaceous glands and their
secretions. These patients appear to be prone to the development of secondary bacterial
infections, which may contribute significantly to pruritus and hair loss. Hair loss has also
been postulated (based on mouse, sheep and horse studies) to be caused by the lack of
sebaceous secretions, these being necessary to separate the internal root sheath from the
hair shaft; without separation, there seems to be a progression to hair follicle damage and
scarring (3). Biopsy of the skin is usually diagnostic. Affected areas show a
pyogranulomatous inflammation (neutrophils and macrophages) around the sebaceous
glands. Sebaceous glands are in various stages of being destroyed. Marked orthokeratotic
hyperkeratosis present (thickening of stratum corneum). In late stage disease,
inflammation resolves leaving an absence of sebaceous glands.
Because of previous success in the treatment of this disease with the synthetic retinoids 1,4 ,
vitamin A is now used. The oral vitamin A dosage utilized is small to medium-sized dogs
10,000 IU BID; large breeds (Akitas, Standard Poodles) 20,000 IU BID. Tests for tear
production should be routinely done to monitor these dogs, as Vitamin A may rarely
cause keratitis conjunctivitis sicca (KCS); also, trimethoprim-sulfa drugs should not be
given at the same time as Vitamin A, as these may potentiate the possibility of
developing KCS. Treatment of any secondary pyoderma is a necessity. The efficacy of
vitamin A as stand-alone treatment has recently beenquestioned. 5 A recent report
suggests that cyclosporine may also be effective at a dose of 5mg/kg daily. 6 The
Duoxocalm ® Seborrhea Spot-on may be effective in spot treating small areas.

Sebaceous adenitis has also been rarely reported in cats 7 and rabbits 8 , but the best method
of treatment in these species is still uncertain; cyclosporine was successful in one cat. 9
Zinc-responsive dermatosis
Zinc-responsive dermatosis consists of two syndromes. Syndrome I has been identified
in Siberian huskies and occasionally other breeds and is typified by crusting and scaling
of the mucocutaneous junctions, elbows and foot pads. These dogs are thought to have a
genetic defect in zinc absorption from the intestines. Therefore, this disease will often
occur in dogs fed normal, balanced diets. Diagnosis is based on breed, physical
examination and histopathology, which shows marked follicular and epidermal
parakeratotic hyperkeratosis. Treatment is the addition of zinc supplement to the diet
indefinitely. Zinc sulfate, zinc methionine, or zinc gluconate may all be used; a dosage of
2-3 mg of elemental zinc/kg is recommended. Rarely, these dogs seemed to respond
better if an essential fatty acid supplement is also given. A parenteral zinc preparation is
available in Europe. Clinical signs usually are greatly improved within four to six weeks.
Intact females may respond to lower dosages of zinc after being spayed 10 .
Syndrome II occurs in rapidly growing puppies that are often fed poor-quality dog food
or over-supplemented (especially with calcium) diets. These dogs are thought to have a
relative zinc deficiency, possibly caused by a combination of low zinc intake and calcium
or phytate- (plant protein) binding of the zinc. Clinical signs are generalized crusting
plaques with extensive crusting and fissuring of the foot pads. Diagnosis is by history,
clinical signs and histopathology (which resembles that of Syndrome I). Response to
zinc therapy is dramatic, though changing to a balanced diet may be all that is necessary.
Supplementation with zinc is usually not needed after maturity.
Interestingly, zinc-responsive dermatosis has also been reported in the dingo (Canis
dingo) 11 and the red wolf (Canis rufus) 12 .
Superficial necrolytic dermatitis
Also known as SND, hepatocutaneous syndrome, epidermal metabolic necrosis, or
diabetic dermatosis, this disease is being seen with increased frequency in dogs 13 , and has
also been reported in the cat 14 and a red fox (Vulpes vulpes) 15 . The cutaneous lesions
include crusting, erythema, exudation, and alopecia periorally and periocularly, around
the genitals, and the distal extremities, as well as hyperkeratosis and ulceration of the
footpads. The skin disease may precede the onset of the signs of the internal disease.
Histopathologic findings include superficial perivascular-to-lichenoid dermatitis, with
marked diffuse parakeratotic hyperkeratosis and striking inter- and intracellular edema
limited to the upper half of the epidermis (‘red, white and blue sign’). 16 Diagnosis is
usually made by clinical signs, confirmatory histopathology, and an ultra-sound finding
of both hyper- and hypo-echoic areas in the liver (‘Swiss-cheese’ or ‘honey comb’
pattern).

Superficial necrolytic dermatitis resembles the glucagonoma syndrome (necrolytic
migratory erythema) of humans, which is usually associated with hyperglucagonemia and
a glucagon-secreting alpha-cell neoplasm of the pancreas. Hyperglucagonemia has also
been documented in dogs with this syndrome; however, dogs tend to have hepatic
parenchymal damage much more commonly than gluconomas. Dogs with SND have
profoundly low levels of plasma amino acids 13 .
Therapy is best effected with the infusion of amino acids (ex: Amnosyn®) given
intravenously in a central vein, at an approximate rate of 60-80 mg/kg/24 hr. Osmalality
and/or neurologic signs should be monitored (although problems are relatively
uncommon). This is often performed on a daily basis for 2-3 days, and may need to be
repeated on a q 3-6 week basis.
An alternative is the use of oral medications: ProCel® Powder (1 scoop/5kg q12h; Global
Health Products www.globalhp.com 1-800-638-2879), scrambled eggs (? /day),
elemental Zn (2 mg/kg/ day), and sAME (or similar liver protectants).
When the underlying disease can be treated (drug-induced hepatopathy, removal of
glucagonoma) and secondary skin infections (bacterial and/or yeast) are treated, these
dogs have usually responded well for variable lengths of time, sometimes for more than
one year.
Feline Pansteatitis
Pansteatitis is caused by the consumption of high levels of unsaturated fatty acids and/or
the insufficient intake of vitamin E, leading to inflammation of adipose tissue. 17-19 This
disease usually has been related to fish-based diets. However, non-conventional diets
such as pig brains have also been implicated. 20 The disease has also been reported in a
lion (Felis leo). 21
Clinical signs include painful, nodular-to-irregular subcutaneous masses and draining
tracts, pain on abdominal palpation (due to involvement of the abdominal fat),
inappetence, depression and fever, though not all signs will be present in all cats. Less
commonly ascites, pleural effusion, subcutaneous edema may be present. Neutrophilia
and leukocytosis are common findings. Grossly, adipose tissue may be yellow or
discolored, and firm to hard (dependent on the presence of mineralization). Histological
examination shows necrosis of fat cells, severe inflammation of the interstitial tissue with
neutrophils, giant cells and macrophages containing acid-fast droplets of ceroid
pigment. 17,18 Treatment has been reported as vitamin E (alpha-tocopherol 50 mg/kg q24
h), prednisolone (1 mg/kg q12 h), and changing the diet to a fish-free, balanced cat
food. 17 Pain management is very important! Even with these treatments, 25% or more of
these cats will die or be euthanized due to poor response.
References
1. White SD, Rosychuk RAW, Scott KV, et al. Sebaceous adenitits in dogs and

esults of treatment with isotretinoin and etretinate 30 cases (1990-1994). J Am
Vet Med Assoc 1995; 297: 197-200.
2. Rosser EJ, Dunstan RW, Breen PT, et al. Sebaceous adenitis with hyperkeratosis
in the standard poodle: a discussion of 10 cases. J Am Anim Hosp Assoc 1986; 23:
341-5.
3. Stenn KS, Sundberg JP, Sperling LC. Hair follicle biology, the sebaceous gland,
and scarring alopecias. Arch Dermatol 1999;135:973-4.
4. Stewart LJ, White SD, Carpenter JL. Isotretinoin in the treatment of
sebaceous adenitis in two viszla dogs. J Am Anim Hosp 1991; 27:65-71.
5. Lam ATH, Affolter VK, Gericota B, White SD. Oral vitamin A in the treatment
of canine sebaceous adenitis. Veterinary Dermatology 20:223.
6. Linek M, Boss C, Haemmerling R, et al. Effects of cyclosporine A on clinical and
histologic abnormalities in dogs with sebaceous adenitis. J Am Vet Med Assoc
2005; 226:59-64.
7. Scott, DW. Adénite sébacée pyogranulomateuse sterile chez un chat. Pointe Vet
1989; 21: 107-11.
8. White SD, Linder, K, Shultheiss P et. al. Sebaceous adenitis in four domestic
rabbits (Oryctolagus cuniculus). Vet Dermatol; 11: 53-61, 2000.
9. Noli C, Toma S. Three cases of immune-mediated adnexal skin disease treated
with cyclosporin.Vet Dermatol 2006;17:85-92.
10. White SD, Bourdeau P, Rosychuk RAW et al. Zinc-responsive dermatosis in
dogs: 41 cases and literature review. Vet Dermatol 2001, 12: 101-110.
11. Stringfield, C. Case Report: Amber Girl. Zoo View 1997; 31 (2): 14-5.
12. Kearns K, Sleeman J, Frank L, Munson L. Zinc-responsive dermatosis in a red
wolf (Canis rufus). J Zoo Wildl Med 2000; 31: 255-258.
13. Outerbridge CA, Marks SL, Rogers QR. Plasma amino acid concentrations in 36
dogs with histologically confirmed superficial necrolytic dermatitis. Vet Dermatol
2002; 13:177-186.
14. Kimmel SE, Christiansen W, Byrne KP. Clinicopathological, ultrasonographic,
and histopathological findings of superficial necrolytic dermatitis with
hepatopathy in a cat. J Am Anim Hosp Assoc. 2003; 39:23-27.
15. Van Poucke S, Rest JR. Superficial necrolytic dermatitis associated with hepatic
lipidosis in a red fox (Vulpes vulpes). Vet Rec 2005;156:54-55.
16. Gross TL, Song MD, Havel PJ, et al. Superficial necrolytic dermatitis (necrolytic
migratory erythema) in dogs. Vet Pathol 1993; 30: 75-81.
17. Tidholm A, Karlsson I, Wallius B. Feline pansteatitis: a report of five cases. Acta
Veterinaria Scandinavica 1996; 37: 213–217.
18. Koutinas AF, Miller WH, Kritsepi M et al. Pansteatitis (steatitis, ‘yellow fat
disease’) in the cat: a review article and report of four spontaneous cases. Vet
Dermatol 1993;3:101–106.
19. Summers BA, Sykes G. Pansteatitis mimicking infectious peritonitis in a cat.
Journal of the American Veterinary Medical Association 1982;180:546–549.
20. Niza MM, Vilela CL, Ferreira LM. Feline pansteatitis revisited: hazards of
unbalanced home-made diets. J Feline Med Surg 2003;5:271-277.
21. Bone WJ. Pansteatitis in a lion (Felis leo). J Am Vet Med Assoc 1968;153:791-
792

DISEASES THAT CAN FOOL US
PART 2 PARANEOPLASTIC SYNDROMES AND CUTANEOUS NEOPLASIA
Feline paraneoplastic alopecia is a ventral alopecia in which the abdominal skin appears
to glisten (but is not fragile), may have a secondary Malassezia infection, and has also
been associated with dry, fissured foot pads 1 . Necropsy usually reveals an exocrine
pancreatic adenocarcinoma, often with metastases to the liver and elsewhere. One cat
with a bile duct carcinoma has also been described. Temporary resolution of the skin
disease has been reported in one cat which had the primary tumor removed; the lesions
recurred following metastases of the tumor 2 . Histology of the skin shows severe atrophy
and miniaturization of the hair follicles.
Nodular dermatofibrosis syndrome in German shepherd dogs and occasionally other
breeds associated with renal cystadenocarcinomas or cystadenomas has been reported 3 .
Histologic study of the nodules reveals dense collagen fibrosis. These nodules are most
often found on the distal extremities. Diagnosis of renal lesions is best done by
ultrasound. This should be repeated at six month intervals if the disease is suspected but
the original ultrasound is normal. While the prognosis is serious, some dogs with benign
renal cysts have survived for five years or more after diagnosis 4 . Recent data in the
German Shepherd dogs suggest that the syndrome may be caused by a mutation in a
previously unidentified tumor suppressor gene 5 .
Thymomas have been associated with an exfoliative dermatitis described in older (often
‘orange’) cats. 6 The exact mechanism is unknown, but an erythema multiforme-type
reaction has been proposed. If detected, the tumor’s removal will lead to resolution of
signs. Recently, radiotherapy has been reported as a therapeutic option. 7,8
Cutaneous lymphosarcoma occurs in older dogs (although young dogs are occasionally
affected) with no sex predilection but with a predilection for boxers, cocker spaniels,
beagles, German shepherds, golden retrievers and Scottish terriers. It is very rare in cats.
Cutaneous lymphosarcoma is usually generalized or multifocal and may present as
nodules, plaques, ulcers, erythroderma and/or exfoliative dermatitis. It may occur with or
without other systemic involvement. Pruritus is very common.
Histologically, cutaneous lymphosarcoma in the dog can be divided into epitheliotropic
and nonepitheliotropic types. Epitheliotropic (following or "hugging" the epidermis
histologically) forms of cutaneous lymphosarcoma have been shown in the dog to usually
be of T lymphocyte origin while nonepitheliotropic forms are usually of B lymphocyte
origin. Nonepitheliotropic lymphosarcomas are characterized by diffuse dermal and
subcutaneous infiltration by malignant lymphocytes. The epitheliotropic form is often
termed ‘mycosis fungoides’. It often begins as a generalized pruritic exfoliative
dermatitis or erythroderma and progresses over a variable length of time (weeks to
months) to nodules and plaques, ultimate systemic involvement and death. Canine
mycosis fungoides also may have a primarily mucocutaneous distribution.

Clinical management of cutaneous lymphosarcoma, with or without concurrent systemic
involvement, is difficult. Without treatment, most dogs presented to a referral center are
euthanized within one month of diagnosis. Response to standard chemotherapeutic
protocols used in lymphosarcoma of other organ systems have been disappointing; 40%
to 50% success rate may be seen using isotretinoin (Accutane), 3-4 mg/kg/day 9 .
Prednisone (1 mg/kg/day) may alleviate some of the pruritus. Recently, lomustine
(CCNU), an alkylating agent, has been effective in the treatment of dogs with cutaneous
lymphoma, at a dose of 50mg/m 2 q 21-30 days 10 . Remission lasted from 2-15 months.
Neutropenia may be seen, and is most likely to occur 1-2 weeks after treatment, although
this has usually been noted with higher doses 11 . While generally a safe drug, irreversible
hepatic toxicity (again, generally at higher doses) has been reported 12 .
Metastatic Pulmonary Carcinomas
This problem has been reported in cats: the lesions occur on the distal extremities,
especially the front feet, and look more like inflammatory pododermatitis than a
neoplastic process 13 . Their presence may be noted before pulmonary signs are noted.
Rarely, the neoplasm may metastasize to other areas on the body, such as the abdominal
skin 14 . The neoplasm may be either a bronchogenic or squamous cell carcinoma.
Paliative treatment to reduce the discomfort may be attempted (topical or systemic
corticosteroids to reduce edema, etc).
References
1. Pascal-Tenorio A, Olivry T, Gross TL, et al. Paraneoplastic alopecia associated
with internal malignanacies in the cat. Vet Dermatol 1997; 8:47-52.
2. Turek MM. Cutaneous paraneoplastic syndromes in dogs and cats: a review of the
literature. Vet Dermatol 2003;14 :279-96.
3. Suter M, Lott-Stolz G, Wild P. Generalized nodular dermatofibrosis in six
Alsatians. Vet Pathol 1983;20:632-4.
4. White SD, Rosychuk RAW, Shultheiss P, et al. Nodular dermatofibrosis and
cystic renal disease in three mix-breed dogs and a boxer. Vet Dermatol, 9:119-26,
1998.
5. Jonasdottir TJ, Mellersh CS, Moe L, et al. Genetic mapping of a naturally
occurring hereditary renal cancer syndrome in dogs. Proc Natl Acad Sci U S A.
2000 11;97:4132-7.
6.. Scott DW, Yager JA, Johnston KM. Exfoliative dermatitis in association with
thymoma in three cats. Fel Pract 1995; 23(4) 8-13.
7. Kaser-Hotz B, Rohrer CR, Fidel JL, et al. Radiotherapy in three suspect cases of
feline thymoma. J Am Anim Hosp Assoc 2001; 37:483-488.
8. Smith AN, Wright JC, Brawner WR Jr, et al. Radiation therapy in the treatment of
canine and feline thymomas: a retrospective study (1985-1999). J Am Anim Hosp
Assoc 2001; 37:489-96.
9. White SD, Rosychuk RA, Scott KV, et al. Use of isotretinoin and etretinate for
the treatment of benign cutaneous neoplasia and cutaneous lymphoma in dogs. J
Am Vet Med Assoc 1993; 202: 387-91.

10. Graham JC, Myers RK. Pilot study on the use of lomustine (CCNU) for the
treatment of cutaneous lymphoma in dogs. Proceedings of the 17 th ACVIM
meeting, Chicago Illinois, 1999, p 723.
11. Moore AS, London CA, Wood CA, et al. Lomustine (CCNU) for the treatment of
resistant lymphoma in dogs. J Vet Intern Med 1999;13: 395-398
12. Kristal O, Rassnick KM, Gliatto JM, et al. Hepatotoxicity associated with CCNU
(lomustine) chemotherapy in dogs. J Vet Intern Med 2004;18: 75-80.
13. Gottfried SD, Popovitch CA, Goldschmidt MH, et al. Metastatic digital
carcinoma in the cat: a retrospective study of 36 cats (1992-1998). J Am Anim
Hosp Assoc 2000;36:501-509.
14. Favrot C, Degorce-Rubiales F. Cutaneous metastases of a bronchial
adenocarcinoma in a cat. Vet Dermatol 2005;16:183-186.

DISEASES THAT CAN FOOL US
PART 3 ISCHEMIC DERMATOSES, ERYTHEMA MULTIFORME and RARE
CUTANEOUS DISASTERS
Ischemic dermatoses fall into three categories: dermatomyositis, vaccine- and drug-
caused cases, and idiopathic. Dermatomyositis has been reported primarily in collies and
Shetland sheepdogs and their crosses, although other breeds have a sporadic incidence of
this disease 1-3 . As its name implies, the disease affects both the muscles and the skin.
Cutaneous changes include crusts, ulcerations, vesicles, and/or alopecia around the mucocutaneous
junctions, front legs, ear tips, and tail, though other body areas may be
affected. Claws may be misshapen. Muscular atrophy may be generalized or may be
selective, often affecting the temporal and masseter muscles. Clinical manifestations
vary, with some dogs showing only skin or muscular signs, while in others both systems
are affected. Serum enzymes such as creatinine phosphokinase (CPK) are usually
normal, and muscle involvement often may be proved only by biopsy or
electromyography. Skin biopsies generally reveal perifollicular mononuclear
inflammation, and occasionally show intracellular edema of the basal cell layer of the
epidermis, with subepidermal clefts; advanced cases show a loss of the normal follicular
structures. Dermal blood vessels may be decreased in number, be over-distended,
smudged, hyalinized and/or sclerotic in appearance. The onset of clinical signs usually
occurs before the age of 6 months. The severity of the disease varies greatly, with some
dogs improving with age. Females should be spayed as estrus may exacerbate clinical
signs. Diagnosis is based on clinical signs and skin biopsy. Recently, the disease in
Shetland Sheepdogs has been linked to a change in chromosome 35 4 .
Drug- or vaccine induced ischemic dermatosis is most commonly associated with
rabies vaccination, manifesting itself as alopecia, scale and crusts, and occasionally
ulceration, in the area of the vaccine administration, and rarely, in other places as well
(especially the pinnal margins and tail tip. Diagnosis is by clinical signs and biopsy.
Histology shows involuting, small hair follicles with prominent connective tissue
associated with the external root sheaths – the follicles will sometimes disappear
permanently. Deep dermal vessels will show a plasmacytic/lymphocytic vasculitis; more
superficial vessels will appear as noted above for dermatomyositis 5 .
Idiopathic ischemic dermatosis can occur at any age and any canine breed. Typically,
the tail tip, ear margin, face (nasal planum) and sometimes trunk are affected. Claws may
be misshapen. Histopathology is as for the vaccine caused type. Recently, there have
been anecdotal reports of dogs with this disease having positive Ehrlichia titers and
responding completely to doxycyclines – this is probably worth pursuing.
Pentoxifylline (PTX) 10-20 mg/kg q8h, is often effective in controlling ischemic
dermatoses. PTX is derived from theobromine. Pentoxifylline, and other
methylxanthines produce anti-inflammatory effects. PTX also improves blood flow
through narrowed arteries because of the rheological property which allows red blood
cells to change shape. It is not known if the improvement in patients with ischemic

dermatoses are caused by improved blood flow or via the anti-inflammatory mechanisms.
Vomiting is occasionally seen as a side-effect.
Erythema multiforme (EM) is an acute eruption of the skin and mucous membranes. It
is characterized in human beings clinically by annular ("target") lesions. While these
have been observed in animals, more common signs are mucocutaneous vesicles, ulcers,
maculae, and/or urticarial plaques may also be seen. In widespread lesions, the ventrum
and peri-ocular areas are often involved. EM may be self-limiting, although by the time
the animals arrive at the specialist’s office, this is not often the case. EM histologically
shows apoptotic (programmed-cell death mechanism-activated) keratinocytes, with
satellitosis (lymphocytes surrounding the keratinocytes, presumably triggering the
programmed cell death mechanism). The incidence/recognition of this disease seems to
be increasing. While erythema multiforme has been reported to have an association with
drug eruptions, recent work points to TEN (see below) and ‘cross-over syndromes’
between the two diseases as more likely to be due to drug involvement 6 . Viruses have
also been hypothesized to cause EM in small animals, and there is one report of EM
caused by parvo virus in a puppy 7 . The author has seen a few cases that seemed to have
an ischemic component, or occurred concurrently with an ischemic dermatitis. While
theoretically pentoxifylline should be helpful, the author has seen 2 dogs which had EM
induced by pentoxifylline! Intravenous human immunoglobulin has been reported as
successful in two dogs when infused on 2 consecutive days (1 g/kg per day) 8 . This is a
relatively expensive treatment.
Rare Disaster Syndromes
These include 4 rare conditions which are often typified by neutrophils in the skin, and 1
by eosinophils in the skin, but with different underlying causes, and therefore treatments.
Necrotizing fasciitis (‘flesh-eating’ bacteria) caused by Streptococcus canis (biotype 3).
Dogs present with fever, swelling, erythema, disproportionate pain on palpation, draining
tracts and ulcers. There may be pockets of fluid, usually malodorous. It has been
hypothesized that Great Danes and Sharpeis may be predisposed, but too few cases have
been reported in the literature to confirm this. There is rapid progression of this disease,
as there is of all three diseases in this group. Diagnosis is by clinical signs, skin biopsy
and bacterial culture and susceptibility; imaging such as ultrasound, CT scan and/or MRI
may be helpful (if available) to find exudates advancing along fascial planes that may not
be evident on physical examination. Treatment is widespread surgical debridement and
antibiotics – eventually based on susceptibility results, but initially with clindamycin
and/or amoxicillin-clavulanate, plus an aminoglycoside. 9 Do not use fluoroquinolones, as
these have been associated with possibly engendering or enhancing the extreme toxicity
of these Streptococcus strains. 10 NSAIDS should also be avoided, as there is some
evidence they may suppress neutrophil activity and mask clinical signs. 11
Sweet’s (sterile neutrophilic dermatosis) syndrome is a non-infectious, presumed immune
mediated condition typified by erythema, fever, malaise, neutrophilia, lameness and
nuetrophilic effusions into the joints. This is also a rapidly progressive disease, and may

e caused by certain medications 12 , as well as arising spontaneously. There is one report
of a dog with internal organ involvement. 13 Diagnosis is based on skin biopsy, the lack of
bacteria on culture of intact skin lesions or joint aspirates, and response to corticosteroids
(prednisolone 1 mg/kg bid initially).
Sterile Pustular Erythroderma of Miniature Schanuzers
A rare, severe, often fatal disease, seemingly limited to miniature Schnauzers, often
preceded by bathing. This condition presents with severe depression and malaise, often
with fever. Skin lesions are (often dramatic) erythema, pustules or epidermal collarettes,
and/or wheals. These dogs are very sick – treatment, when successful, consists of high
dose corticosteroids. 14 In a recent abstract, a contact reaction to one of the components in
an aloe-based shampoo was implicated. 15
Staphylococcal Toxic Shock is caused by Staphylococcus sp, presumably Spseud-
intermedius. Erythema, fever, malaise, and neutrophilia are seen initially; the malaise
may be severe and edema of the legs may develop as the disease progresses. This may be
the most rapidly progressing of these three diseases. Diagnosis is based on clinical signs
– a skin biopsy and bacterial susceptibility should be performed, but any suspicion on the
veterinarian’s part for this disease should initiate the immediate use of staphylocidal
antibiotics – cephalosporins have been recommended. Pugs may be over-represented. 14
Well’s like syndrome is a eosinophilic, generalized dermatitis to cellulitis. It has been
associated with either GI signs and/or drugs in some, but not all cases. Peripheral
eosinophilia is rare. Skin lesions are papules, macules, and erythema. Pruritus is variable.
Histopathology shows an eosinophilic dermatitis, often with eosinophilic ‘flame figures’
(collagen surrounded by eosinophils or their granules). Treatment consists of
prednisolone/prednisone at 1-2 mg/kg, then tapered. Treatment duration is variable, but
should be continued for at least one month. 16,17
References
1. Hargis AM, Mundell A. Famillial canine dermatomyositis. Comp Cont Ed Pract
Vet 1992; 14:855-65.
2. Hargis AM. A skin disorder in three Shetland sheepdogs: comparison with
familial canine dermatomyositis of Collies. Compend Cont Ed Pract Vet 1985;
7:306-15.
3. White SD, Shelton D, Sisson A, et al. Dermatomyositis in an adult Pembroke
Welsh corgi. J Am Anim Hosp Assoc 1992; 28:398-401.
4. Clark LA, Credille KM, Murphy KE, et al. Linkage of dermatomyositis in the
Shetland Sheepdog to chromosome 35. Vet Dermatol 2005;16:392-394.
5. Vitale CB, Gross TL, Magro CM. Vaccine-induced ischemic dermatopathy in the
dog. Vet Dermatol 1999; 10:131-142.
6. Hinn AC, et al. Erythema multiforme, Steven-Johnson syndrome, and toxic
epidermal necrolysis in the dog: clinical classification, drug exposure, and
histopathological corelations. J Vet Allergy and Clinical Immunology 1998 6:13-
20.

7. Favrot C, Olivry T, Dunston SM, et al. Parvovirus infection of keratinocytes as a
cause of canine erythema multiforme. Vet Pathol. 2000 37: 647-9.
8. Trotman TK, Phillips H, Fordyce H, et al. Treatment of severe adverse cutaneous
drug reactions with human intravenous immunoglobulin in two dogs. J Am Anim
Hosp Assoc 2006; 42:312-320.
9. Naidoo SL, Campbell DL, Miller LM, et al. Necrotizing fasciitis: a review.
J Am Anim Hosp Assoc 2005 ;41:104-9.
10. Ingrey KT, Ren J, Prescott JF. A fluoroquinolone induces a novel mitogenencoding
bacteriophage in Streptococcus canis. Infect Immun 2003 ;71:3028-
3033.
11. Csiszer AB, Towle HA, Daly CM. Successful treatment of necrotizing fasciitis in
the hind limb of a Great Dane. J Am Anim Hosp Assoc 2010; 46:433-8
12. Mellor PJ, Roulois AJ, Day MJ et al. Neutrophilic dermatitis and immunemediated
haematological disorders in a dog: suspected adverse reaction to
carprofen. Journal of Small Animal Practice 2005; 46: 237–42.
13. Johnson CS, May ER, Myers RK, et al. Extracutaneous neutrophilic inflammation
in a dog with lesions resembling Sweet's Syndrome. Vet Dermatol. 2009; 20:200-
5.
14. Gross TL, Ihrke PJ, Walder EJ, Affolter VK. Skin Diseases of the Dog and Cat.
2 nd ed. Blackwell Publishing, Oxford, UK. 2005; 20-22, 84-86, 366-388.
15. Murayama N, et al. A case report of superficial suppurative necrolytic dermatitis
of miniature Schnauzers with an identified causative agent using patch testing.
Proceedings of the North American Veterinary Dermatology Forum, 2008, pg
197.
16. Holm KS, Morris DO, Gomez SM, et al. Eosinophilic dermatitis with edema in
nine dogs, compared with eosinophilic cellulitis in humans. J Am Vet Med Assoc
1999; 215:649-653.
17. Mauldin EA, Palmeiro BS, Goldschmidt MH, et al. Comparison of clinical history
and dermatologic findings in 29 dogs with severe eosinophilic dermatitis: a
retrospective analysis. Vet Dermatol 2006; 17:338-347.