penfigo artigo

© 2006 The Author. Journal compilation © 2006 European Society of Veterinary Dermatology.

17

; 291–305

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Blackwell Publishing Ltd

Review

A review of autoimmune skin diseases in domestic

animals: I – Superficial pemphigus

Thierry Olivry

Center for Comparative Medicine and Translational Research and Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina, USA Correspondence: Thierry Olivry, Department of Clinical Sciences, North Carolina State University, College of Veterinary Medicine, Research Building, 4700 Hillsborough Street, Raleigh, NC 27606, USA. E-mail: [email protected]

Abstract

In humans, the pemphigus denomination encompasses

a group of autoimmune blistering skin diseases with

intraepidermal separation resulting from cell–cell

detachment by acantholysis. Entities are classified

based on the level of blistering in the epidermis, and

both superficial (pemphigus foliaceus, IgA pemphigus)

and deep (pemphigus vulgaris, pemphigus vegetans

and paraneoplastic pemphigus) variants are recognized.

In domestic animals, subsets of pemphigus have been

recognized since the mid-1970s, and the disease classi-

fication resembles that used for human patients. This

article reviews up-to-date knowledge on the epide-

miology, clinical signs, histopathology, immunopathology

and treatment outcome of superficial pemphigus in

domestic animals. Detailed information on canine,

feline, equine and caprine pemphigus foliaceus, canine

and feline pemphigus erythematosus and canine

panepidermal pustular pemphigus is provided.

Accepted 01 August 2006

Introduction

Epidermal cells possess structures that are involvedeither in cell–cell (desmosomes) or in cell–matrix adhesion(hemidesmosomes-anchoring fibrils complex). Wheneverautoantibodies target proteins in these adhesion struc-tures, intra- or sub-epidermal separation often occurs, andclinical signs of an autoimmune blistering skin diseaseusually develop.

1

In the last 30 years, the identification ofantigens targeted by circulating autoantibodies has helpedreshape the classification of autoimmune blistering skindiseases in humans. Based on clinical signs, histopathologyand immunological characteristics, several entities are nowwell recognized. For example, the most common diseasesassociated with autoantibodies against epidermal basementmembrane antigens are bullous pemphigoid (target: collagenXVII), mucous membrane pemphigoid (laminin-5, collagenXVII, integrin alpha-6 beta-4) and epidermolysis bullosa

acquisita (collagen VII).

1

Similarly, autoantibodies targetingdesmosomal proteins in keratinocytes may result inblistering diseases of the pemphigus group. This groupencompasses both deep (pemphigus vulgaris: desmoglein-3

±

desmoglein-1; paraneoplastic pemphigus: desmoglein-3, plakins) and superficial variants (pemphigus foliaceus:desmoglein-1; IgA pemphigus, desmocollin-1 and 3).

1

In animals, autoimmune blistering skin diseases werefirst recognized 30 years ago, with the seminal descriptionof pemphigus vulgaris in dogs.

2,3

Since then, most animalhomologues of the human entities have been identified. Itis the aim of the forthcoming series of reviews to compilethe latest knowledge on autoimmune skin diseases knownin domestic animal species. The first monograph of thisseries covers information on the epidemiology, clinicalsigns, treatment outcome, pathology and immunology ofsuperficial variants of pemphigus in dogs, cats, horses andgoats. Diseases highlighted herein are pemphigus foliaceus(PF), pemphigus erythematosus (PE) and the so-called‘panepidermal pustular pemphigus’ (PPP).

Pemphigus foliaceus

History

The first article describing the existence of PF in dogs waspublished in 1977 by Halliwell and Goldschmidt.

4

Sincethen, this canine disease has been reported worldwide incountless articles, each reporting one or few cases. Onlythree retrospective studies of large series of subjects (37,26 and 91 cases) have been published in English.

5–7

Thefirst report of feline PF was in 1982,

8

and there are onlytwo papers describing more than 10 cases each.

6,9

Pem-phigus foliaceus was recognized in horses in 1981,

10

andthree articles report multiple patients.

6,11,12

Finally, PF is arare autoimmune disease of goats and only scatteredreports exist.

13–16

Incidence and prevalence

Very little epidemiological information on canine PF isavailable, unfortunately. In a veterinary teaching hospital(New York State College of Veterinary Medicine at CornellUniversity), PF was diagnosed in 26 of 9750 dogs between1975 and 1984. This proportion results in an estimatedincidence of PF of approximately three per 1000 caninepatients referred for skin diseases per year.

6

In anotherinstitution (Michigan State University College of VeterinaryMedicine), PF was the diagnosis made in 1% of surgicalskin biopsies read by veterinary pathologists (R. W.Dunstan, personal communication, WSAVA meeting, 1997).Finally, in a retrospective study of 84 dogs with auto -immune skin diseases, PF was the diagnosis given to26 subjects, nearly one third of all dogs with autoimmuneskin diseases.

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From data published in one article, the incidence offeline and equine PF could be calculated as five and 10 per1000 patients per 10 years, respectively.

6

Pemphigusfoliaceus is too rare in goats to estimate its prevalence andincidence.

Signalment

Genetic factors are likely to predispose to the developmentof canine PF. Indeed, data gathered from several studiessuggest that PF is more frequently diagnosed in dogs fromcertain breeds. For example, in one group of 37 dogs withPF, six breeds (bearded collie, Akita, Newfoundland,Schipperke, Doberman and Finnish Spitz) exhibited a sig-nificant risk to develop the trait compared to the controlpopulation.

5

However, only two of these breeds (Dobermansand Akitas) had more than one representative affected,and both breeds exhibited a high odds ratio (OR) to developPF (OR = 29).

5

In a second group of 26 dogs,

6

Akitas anddachshunds were the only breeds with more than oneindividual diagnosed with PF. For dogs reported in thisarticle, we calculated the OR for PF development in Akitasto be 3.0 with a large confidence interval (0.7–12.9).

6

Usingdata from the University of Pennsylvania Veterinary Hos-pital, breeds at significant risk of PF development includedAkitas (OR = 38; 95% confidence interval: 13–99), Englishcocker spaniels (21; 8–88), chows (12; 4–49), shar-peis (8;2–30) and collies (4; 2–14). Finally, in a University surgicalpathology service, three breeds of dogs accounted for onethird of all cases of PF, and OR for the diagnosis of PF were23, 16 and 7 in Akitas, chows and Australian shepherds,respectively (R. W. Dunstan, personal communication,WSAVA meeting, 1997). Interestingly, two female Shetlandsheepdog littermates were reported to develop PF simul-taneously at 6 months of age.

18

In summary, over the yearsand in various geographical locations in the USA, chowsand Akitas appear to be at high risk to develop PF. Thiscommon predisposition may not be surprising in light ofthe recent discovery that these two breeds exhibit closelyrelated genotypes and are in close phylogenetic linkage.

19

In the three largest case series of dogs with PF, themale to female sex ratios were 13:24 (0.5), 14:12 (1.2) and46:45 (1.0), and these proportions suggest that a sex pre-disposition is unlikely to occur in this species.

5–7

In thesereports, the age of onset of canine PF was very variable,as it ranged from less than one up to 16 years (means: 4.2,6 and 6 years).

5–7

A breed predisposition for PF has not been reporteddefinitively in the feline species even though domesticshort-haired cats were found to be most commonly affectedwith this disease in two case series.

6,9

The male to femalesex ratios were 5:5 and 27:30, suggesting that a sexpredisposition for development of PF in cats also wasunlikely.

6,9

In these two studies, the age of onset of felinePF ranged from less than 1 to 9 and 17 years, respectively(medians: 5 years).

6,9

In the first study of equine PF, Appaloosas accounted forone third of the patients, a proportion five times higherthan that of the general equine hospital population.

6

How-ever, such breed predisposition was not confirmed in theother two case series.

11,12

In none of these three paperswas a sex predisposition apparent.

6,11,12

While no articlereported an age predilection for disease development, all

studies found that PF could affect both very young (lessthan 6 months) and ageing horses of up to 25 years old.

6,11,12

Finally, there are too few cases of caprine PF for assem-bling relevant information on breed, sex and age predis-position to disease development.

Triggering factors for PF

Environmental factors are suspected to induce flares ofcanine PF. One of such factors may be sunlight exposure.A decade ago, a book chapter reported a seasonal exacer-bation of the disease with more active flares and requirementfor higher immunosuppressive drug dosages in warmermonths, but evidence to support such claims unfortunatelywas not provided.

20

In contrast to this assertion, a seasonalpattern of PF development was not found in an epidemio-logical study regrouping 66 dogs with PF.

21

More recently,Japanese investigators reported that lesional scores of PFworsened in the summer in 10/12 dogs studied, while valuesimproved in the winter.

22

Experimentally, irradiation ofnonlesional skin from a dog with facial-predominant super-ficial pemphigus with 45–90 kJ m

−

2

of ultraviolet B (UVB)led to epidermal acantholysis after 1 day.

In vitro

, incuba-tion of pemphigus serum on UVB-irradiated skin explantsresulted in more intense intragranular acantholysis than onnon-irradiated cell cultures.

23

The latter findings suggestthat additional studies on UV exacerbation of caninesuperficial pemphigus are warranted.

In horses with PF, a higher risk for flares during fall andwinter months was reported in one study,

12

but a clearseasonal pattern was not observed in the second series ofcases.

11

In two of these 15 horses, however, signs wereobserved to recur each summer.

11

A higher incidence of PF in dogs with allergic skin dis-eases has been mentioned, but evidence supporting suchan association was not given.

20

Interestingly, a previoushistory of flea allergy dermatitis was the most commonskin disease reported in dogs later diagnosed with PF inone study from California.

21

This observation must betaken with caution because of the high prevalence of fleaallergy dermatitis in that particular geographical location.

In humans, several drugs are suspected to either cause‘pharmacological’ acantholysis (i.e. drug-induced pemphigus)while others can stimulate disease flares in patients alreadypredisposed to develop this illness (i.e. drug-triggeredpemphigus).

24

Cases of drug-related PF have been sus-pected in several dogs and rare cats for 20 years.

9,25–29

Arecent paper provided information on four additionalpatients.

30

In these four dogs, the diagnosis of drug-relatedPF was based on history, clinical signs, histopathology andresponse to withdrawal of suspected causative drug(s). Inthis paper, however, one subject (case 1) was treated withimmunosuppressive doses of prednisolone and azathioprinefor 7.5 months, another (case 2) was given high dosagesof prednisolone for 8.5 months, the last patient receivedlow dosages of prednisone for 7 months, whereas case 3was not treated with anti-inflammatory medications.

30

Inthat report therefore two of four patients needed monthsof immunosuppression to maintain remission before alldrugs were discontinued. While one cannot discount theauthors’ hypothesis that their patients were affected withdrug-related pemphigus, one cannot disprove the contra-hypothesis either. Indeed, it is conceivable that the animals


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Superficial pemphigus in domestic animals

mentioned above could have suffered from natural auto-immune PF that went into prolonged remission after immu-nosuppression was discontinued, as has been shownrecently in several dogs with PF.

31

To evaluate the probability of association between theadministration of a medication and the development of aparticular event, an assessment of likelihood of drug re-action must be made using ‘adverse drug reaction probabilityscales’ such as the one developed years ago by Naranjo

et al

.

32

When this scale is applied to all previous cases ofputative drug-related pemphigus in dogs and cats

25–30

onlylow scores interpreted as ‘possible’ probabilities of drugreaction are obtained. Therefore, at this time, the strengthof evidence supporting drug causation for rare cases of PFin dogs and cats is weak at best, and further documenta-tion of canine and feline cases with highly probable drug-related PF is critically needed.

Clinical signs

Clinical signs of PF appear to be similar across domesticanimal species. In most dogs, lesions initially appear onthe face, principally on the dorsal muzzle, planum nasale,periocular skin and ears.

5,6

In these areas, the pattern usu-ally is strikingly bilateral and symmetrical (Fig. 1).

5

In thelargest case series, lesions were restricted to the face in15 of 91 dogs (16%) (Fig. 2).

7

In rare canine patients, thedermatosis exhibits a generalized distribution from theonset, but in most cases, lesions will develop towardsregionalization (Fig. 3) or generalization (Fig. 4) over 3 to 12months.

5,7

In the largest retrospective study, generalizedskin lesions were present in 60/91 dogs (66%), and inthese dogs, crusts were most prevalent on the trunk (58%).

7

A remarkable finding of canine PF is the predilection oflesions for the footpads (Fig. 5).

5

Indeed, footpad involve-

ment is seen in one third of dogs with PF,

7

and rare caninepatients exhibit lesions restricted solely to this location(Fig. 5; right).

6,7,33–36

Of note is that mucosal lesions areonly rarely seen in dogs with PF (2/91; 2%).

7

Pemphigusfoliaceus confined to the claws has been observed in onedog.

37

Figure 1. Canine PF. A 2-year-old chow crossbred dog exhibits crust-ing and erosions bilaterally and symmetrically distributed on the dorsal muzzle, dorsal nasal planum and periocular areas.

Figure 2. Canine facial PF. A 3-year-old Australian shepherd with erythema, erosions, scaling and crusting at the time of initial presentation to the dermatologist (left). Treatment with niacinamide and tetracycline and intermittent oral prednisone led to minimal remission with occasional recurrence of signs (right). During disease flares, superficial pustules (top right; arrowheads) evolved rapidly into crusts overlying erosions (bottom right).

Figure 3. Canine PF (same dog as Figure 1). Skin lesions initially appeared on the face (Figure 1), however, within one week of hair clipping for cruciate ligament repair surgery and following intense sun exposure, PF lesions (pustules, erosions and crusts) erupted on the lateral aspect of the leg where hair had been clipped. Remarkably, there were no lesions on the medial thigh, an area that had been clipped also.

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The nature of skin lesions is comparable in most dogswith PF: transient pustules evolve rapidly into erosionsand crusts, the latter being the lesions most commonlyseen.

5–7

The pustules of PF are usually large and confluent(Fig. 6), and they often exhibit polycyclic borders. Manyhair shafts can protrude from these pustules, in contrastto the lesions of bacterial folliculitis where only a singlehair can be seen coming from each pustule.

38

On rareoccasions, pustules, erosions and crusts are grouped ina unique annular, or polycyclic pattern (Fig. 7).

5,39

Alopeciaand generalized exfoliative erythroderma are seenoccasionally.

5

Pruritus is present in one fourth to onehalf of dogs with PF,

5

whereas systemic symptoms con-sisting of anorexia, depression, fever and weight loss areencountered usually in dogs with widespread erosivelesions.

6

The clinical signs of feline PF are reminiscent of thoseseen in dogs with this disease. Pustules are extremelytransient, however, and the phenotype is dominated byerosions and yellowish crusts on the face (Fig. 8), ears(Fig. 9), and on the feet.

6,8,9,40

Pedal lesions, consisting ofsuppuration or crusts, can be seen on or around the foot-pads or ungual folds of claws (Fig. 10).

6,8,9,35,40

The pheno-type of feline PF is usually mild and fairly localized, butgeneralized lesions can be seen also.

9

The distribution oflesions of feline PF is usually bilateral and symmetrical.

9

Horses with PF usually are presented with multifocal togeneralized crusting, scaling and alopecia affecting theface, neck, trunk and extremities (Fig. 11).

6,11,12

Pustulesare observed rarely, and whenever present, they are

Figure 4. Canine PF. This 3-year-old English bulldog was affected with lesions that progressed rapidly from the face to cover most of the body surface. Inset: details of rapidly drying pustules and crusts from the lateral thigh.

Figure 5. Canine PF. Footpad lesions of canine PF vary with their chronicity. Acute lesions (left) consist of pustules (arrowheads; same dog as in Figure 4), erosions and crusts. With time, crusts coalesce (middle) and dry to form fissures (right).

Figure 6. Canine PF. Large, grouped and often coalescing superficial pustules exhibit a peripheral erythematous halo. Multiple hair shafts protrude from the roof of the pustule (case material: University of California Davis).

Figure 7. Canine PF. Crusts overlie erosions with an erythematous border in a grouped polycyclic arrangement.


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transient.

6,11,12

Skin lesions may exhibit a unique annularpattern as in dogs.

41

Remarkably, ventral oedema is seenin many horses with PF.

12

Systemic symptoms, such asdepression and lethargy, were noticed in 50% of horseswith PF in one study

6

but a similar observation was notmade in another retrospective study.

11

Lesions of equinePF are occasionally painful and/or pruritic.

11,12

In goats, pustules, crusts, scales and alopecia predominateon the face, ventral abdomen, limbs, perineum and tail. Infemale animals, lesions may affect the udder and teats.

13–16

Pemphigus foliaceus in animals has been reported inassociation with systemic diseases such as hypothyroidism,

42

leishmaniasis,

43

thymoma

44

and systemic lupus erythema-tosus.

45

The relationship between PF and these entitiesmay be coincidental, or it could reflect a systemic diseaseprocess leading to the induction of immunological imbal-ances and development of anti-keratinocyte autoimmunity.

Cytology

The diagnosis of PF in animals commences with thedemonstration of acantholytic keratinocytes in impressionsmears of intact pustules (Fig. 12).

5–7

Indeed, isolated to

Figure 8. Feline PF. Alopecia, erosions and crusts developed on the face of a 1.5-year-old Siamese cat during a flare of PF (courtesy of Dr Barbara Atlee).

Figure 9. Feline PF. Yellowish crusts are present on the convex (left) or concave aspects of the pinnae of two cats with PF (left: courtesy of Dr Barbara Atlee; right: case material from the University of California Davis).

Figure 10. Feline PF. Crusting can be seen around footpads and claws (left) or on pads themselves (right).

Figure 11. Equine PF. A 12-year-old quarterhorse mare exhibits erosions and crusts in a figurate pattern on the face and neck (case material from the University of California Davis).

Figure 12. Canine PF. Aspiration cytology from the content of a superficial pustule reveals numerous neutrophils, some eosinophils and scattered isolated or grouped acantholytic keratinocytes (Diff–Quick).

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clustered (e.g. ‘rafts’) free-floating rounded keratinocytesadmixed with nondegenerated neutrophils and rarer eosi-nophils are seen usually.

5–7

Acantholytic keratinocytesexhibit either microscopic characteristics of normal differ-entiated spinous or granular layer epithelial cells, or theypresent signs of apoptosis with eosinophilic cytoplasm,condensed chromatin or karyorrhexis. Occasionally, neu-trophils can be seen in close apposition to detached kerat-inocytes. The presence of acantholytic keratinocytes andneutrophils is not specific of PF, however. Similar micro-scopical findings have been found in canine and equinecases of pustular dermatophytosis, a PF mimicker inwhich

Trichophyton

fungi invade the stratum corneum andinduce subcorneal acantholytic neutrophilic pustules.

46–48

Keratinocyte acantholysis has been reported also in dogswith bacterial skin infections.

38

Histopathology

In dogs, cats, horses and goats with PF, histological exam-ination of lesional skin reveals similar findings. Very earlylesions may be vesicles with acantholytic keratinocytesand scarce neutrophils (Fig. 13). However, these lesionsrapidly evolve into intragranular (Fig. 14) or subcornealpustules (Figs 13,14,15) with isolated and/or clusteredacantholytic cells.

5,6,38,39

In these lesions, neutrophils pre-dominate, but variable numbers of eosinophils may befound.

5–7,38,39

Pustules commonly invade the epitheliumand/or the lumen of the follicular infundibulum.

5,38

In gen-eral, the pustules are large and span the length of multiplefollicular units, a finding that differentiates these lesionsfrom those of bacterial folliculitis.

12,38

Similarly, recornifica-tion, defined as newly reformed stratum corneum at thebase of neutrophilic pustules, is more suggestive of PF(Fig. 16) than bacterial folliculitis.

38

Microscopic character-istics of acantholytic keratinocytes mirror those observedwith cytology. Epidermal cells that recently detached fromtheir neighbours usually appear similar to differentiatedkeratinocytes whilst other cells exhibit cytological charac-teristics of apoptosis.

5

Apoptotic keratinocytes are seenoften in the epidermis of dogs with PF,

49

and as a resultthese apoptotic epidermal cells cannot be taken for bonafide markers of underlying drug reactions. The induction of

apoptosis may reflect the phenomenon of anoikis that fol-lows the rupture of desmosomal cadherin adhesion duringacantholysis.

50

Alternatively, activation of the apoptoticpathway could be an early consequence of the binding of

Figure 13. Canine (left) and feline (right) PF. In these early microscopic lesions, fluid-filled vesico-pustules contain few neutrophils and acantholytic keratinocytes. The sample on the right was obtained as a shave biopsy from an auricular lesion not existing 2 h before (haematoxylin and eosin).

Figure 14. Canine PF. Intraepidermal vesico-pustule in the granular layer of footpad epidermis (haematoxylin and eosin).

Figure 15. Canine PF. Intraepidermal to subcorneal neutrophilic and eosinophilic pustule with single and clustered acantholytic keratinocytes. Of interest is the ‘keratin filament ring’ that can be seen in acantholytic or pre-acantholytic keratinocytes (arrowheads) from the presumed detachment of keratin filaments from desmosomes (haematoxylin and eosin).


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autoantibodies to keratinocytes as shown recently in humanswith pemphigus.

51

Even though acantholytic keratinoc-ytes can be seen in pyogenic skin bacterial infections

38

and pustular dermatophytoses,

46–48

the presence of ahigh number of free-floating epidermal cells, often seen inclusters, may be more suggestive of PF than other infec-tious dermatoses.

38

In one study, immunostaining for desmogleins wasaltered in skin biopsies of dogs with PF compared to thoseof normal individuals.

52

In canine PF skin, desmogleinstaining appeared as distinct clumped deposits at theperiphery of keratinocytes and/or dark cytoplasmic stain-ing of acantholytic cells consistent with internalization ofthese molecules.

52

Immunopathology

Direct immunofluorescenceDirect immunofluorescence (IF) or immunoperoxidasehave been used to detect antikeratinocyte autoantibodiesdeposited in vivo in the skin of animals with PF. Skin-fixedintercellular epidermal IgGs were found in most cats,horses and goats with PF.6,15 Similarly, intercellular epider-mal IgG autoantibodies were detected in 66–80% ofcanine specimens examined (Fig. 17).5,6,17,39,53 One studyestablished that, in some dogs with PF, skin-fixed auto-antibodies belonged to IgG2 and/or IgG4 subclasses.54 In rareinstances, intercellular deposits of IgA or IgM and activatedcomplement (C3 fraction) were observed.6,39 In one thirdof canine specimens, intercellular fluorescence wasrestricted to the upper half of the epithelium.5 In somedogs with PF, direct IF testing of skin biopsy specimenshas remained negative, and these results were attributedto glucocorticoid therapy administered prior to specimencollection.6 Unfortunately, intercellular epidermal IgG alsocan be found in biopsy specimens obtained from dogs withdermatoses other than PF.6,17 These findings markedlyreduce the specificity of direct IF testing for the diagnosisof canine PF.

Indirect immunofluorescenceThe identification of circulating pemphigus autoantibodieshas been performed historically by means of indirect IFtesting of the animal’s sera. For many years, this tech-

nique was deemed unreliable for the diagnosis of animalpemphigus, as circulating IgG autoantibodies rarely werefound in canine, feline or equine sera.6,39 When antikerat-inocyte antibodies were detected in canine PF sera, thetitre was usually inferior to 1 : 40.5,6 A recent study pro-vided information suggesting that indirect IF results willvary according to the substrate utilized for autoantibodydetection. When normal bovine oesophagus substratewas used, circulating antibodies were detected in 65% ofaffected patients.55 Similarly, indirect IF was positive for allcanine PF sera tested on cultured canine keratinocytes.56,57

When other epidermal substrates were employed, how-ever, the frequency of detection of circulating autoantibodieswas usually lower.55 Unfortunately, the skin of the nasalplanum exhibits ‘physiological’ intercellular IgG, renderingindirect IF testing positive using this substrate and normaldog sera.55 At North Carolina State University, indirect IFtesting performed using normal canine footpad revealedantikeratinocyte autoantibody titres superior to 1 : 50 inthe serum of 73 of 87 dogs with PF (84%).58 Using thissubstrate, nearly half of canine PF sera tested wereshown to contain IgG that bound to keratinocytes of bothstratum spinosum and granulosum, but additional IFpatterns also were uncovered.58 These results providedevidence of immunological heterogeneity of canine PF.58

Using neonatal mouse skin as substrates, canine PFserum autoantibodies were detected in 36 of 44 dogs withPF (82%) (Fig. 18), and they were found to be of eitherIgG1 (30/44; 68%) or IgG4 (35/44; 80%) isotypes.59 Similarfindings were reported by other investigators.22 In sixdogs, immunosuppression led to a reduction in clinicalscores with serum IgG, IgG1 and IgG4 autoantibody titresdecreasing in four, one and four patients, respectively.59

Similarly, serum titres of IgG autoantibodies correlatedwith the severity of clinical signs of canine PF in tworecent reports from the same group.22,60

Finally, in one retrospective study, indirect IF testingrevealed circulating antikeratinocyte autoantibodies in 0/9(0%) and 5/9 (56%) cats and horses with PF, respectively.6

Advanced immunological testsUnfortunately, at this time, studies investigating the nature ofautoantigens and pathogenicity of circulating autoantibodiesof feline, equine and caprine PF have not been reported.

Figure 16. Feline PF. Large subcorneal neutrophilic acantholytic pustule with underlying epidermal recornification (haematoxylin and eosin).

Figure 17. Canine PF. Direct IF performed on a frozen skin section reveals intercellular epidermal IgG in the stratum spinosum and granulosum (anticanine IgG fluorescein).

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In contrast, the search for canine PF autoantigens hasbeen ongoing for over 15 years. Limited immunoblottingstudies first revealed that serum IgG autoantibodies fromtwo of two dogs with PF bound to a 148 kDa antigenextracted from lip epithelium.61 In another study, autoanti-bodies from eight of 16 dogs were found to bind a 160 kDaprotein extracted from cultured normal canine keratinoc-ytes.56,62 This 160 kDa antigen was identified also by theserum of a human patient with PF.56 At first, these 148 and160 kDa antigens were suspected to represent differentglycosylation states of canine desmoglein-1 (dsg1), thehomologue of the major PF antigen in humans.

From the late 1990s to mid-2000s, numerous attemptswere made to determine whether dsg1 was, indeed, themain antigen in dogs with PF. The canine dsg1 gene wascloned and sequenced, and it was found to encode apeptide of 1055 amino acid identical in organization to thehuman and bovine genes with highest homology existingin the sequences of the aminoterminal EC1 and EC2segments.63 The extracellular segment of canine dsg1was produced using the baculovirus expression system.64

Remarkably, this recombinant protein was recognized bysera from human patients with PF, but it was not identifiedby IgG from any of the canine PF sera tested.62,65

Recently, human 293T kidney cells were transfected toexpress ectopically membrane-bound canine dsg1. IndirectIF staining established that only five of 83 canine PF sera(6%) recognized canine dsg1-transfected human cells(Fig. 19).66 When present, antidsg1 IgG autoantibodieswere found to target calcium and glycosylation-dependentepitopes.66 In summary, at the time of this writing and in

contrary to previous beliefs, dsg1 appears to be only aminor autoantigen for canine PF.

A second desmosomal cadherin, desmocollin-1, waspursued as a tentative autoantigen for PF in dogs. Caninedesmocollin-1 was cloned, sequenced and producedectopically in transiently transfected Chinese hamsterovary cells.67 Unfortunately, sera from six dogs with PF didnot recognize canine desmocollin-1 isolated from trans-fected cells using immunoprecipitation–immunoblotting.67

Finally, two recent studies provided additional informa-tion relevant to the localization of putative canine PF anti-gen(s). In one dog with nondsg1-specific antikeratinocyteautoantibodies, post-embedding immunoelectron micros-copy confirmed the binding of IgG to the extracellular sec-tion of desmosomes.65 Finally, whatever the autoantigensare, there is evidence for pathogenicity of canine PF IgG.Indeed, the intradermal injection into neonatal mouse skinof IgG isolated from the serum of three dogs with PF ledto acantholytic blistering below the stratum granulosum(Fig. 20).68 Remarkably, acantholysis occurred in theabsence of neutrophil granulocytes in the vesicles.

In summary, at the time of this writing, the identity ofmajor canine PF antigen(s) remains unknown. The identi-fication of these antigen(s) may lead to a more precisereclassification of superficial pemphigus in dogs based onclinical, histopathological and immunological knowledge.

Treatment and outcome

To date, immune suppression remains the initial therapeu-tic intervention of choice for PF in domestic animals. Ofnote is that all recommendations for immunosuppressioninitially were based on interventions used for treatment ofthe human disease, and prospective clinical trials were notperformed to optimize protocols for animals. As a result,information in the following paragraphs was collated almostexclusively from retrospective case series. Historically,standard-of-care treatment of canine PF relied on theinduction of immunosuppression with oral glucocorticoids,such as prednisone or prednisolone, at daily dosages var-ying from 2 to 6.6 mg kg−1 divided in one or two adminis-trations.5–7,69 If lesions decreased in extent and severitywith this regimen, then the dose and/or administration

Figure 18. Canine PF. Serum IgG recognize antigen(s) present on the membrane of superficial epidermal keratinocytes (arrowheads), and also, in some patients, in the cytoplasm of basal and follicular keratinocytes (arrows, bottom) (indirect IF, neonatal mouse skin substrate).59

Figure 19. Canine PF. Only rare sera from dogs with PF recognize canine dsg1 expressed ectopically on the surface of transfected 293T human kidney cells. These results indicate that dsg1 is only a minor antigen in dogs with PF (indirect IF, anticanine IgG-fluorescein).66

© 2006 The Author. Journal compilation © 2006 European Society of Veterinary Dermatology. 299


frequency of glucocorticoids was reduced with the goal ofrapidly achieving alternate day intake.5,69 In many caninepatients, however, glucocorticoid therapy alone appearsincapable in halting or slowing the progression of skinlesions.5 In these cases, cytotoxic drugs are usuallyadded.5,6,69 Azathioprine (2–2.5 mg kg−1, orally, once daily),cyclophosphamide (25 mg m−2, orally, once daily) or chlo-rambucil (0.2 mg kg−1 every 24–48 h) have been proposedas adjunct cytotoxic drugs.5,6,69 Alternatively, immune modu-lation with injectable aurothioglucose (1 mg kg−1 week−1)was used two decades ago to treat dogs with unacceptableside-effects of immune suppressive medications.5,6

Finally, rare dogs with PF exhibit lesions that respond totetracycline and niacinamide (250–500 mg of each, threetimes daily).7,70

In recent years, two small prospective open clinical trialsexplored the efficacy of novel drugs for treatment of dogswith PF. In a 16-week pilot study, eight subjects weretreated with mycophenolate mofetil at 20–40 mg kg−1 perday, divided in three daily doses.71 In three dogs, a reduc-tion of lesional area and/or severity were seen. Four subjectsdid not complete the study and two were euthanized.Additionally, all dogs required concurrent glucocorticoidtherapy to control the severity of skin lesions.71 As a resultof high cost and limited proven benefit, there is currentlyinsufficient evidence for recommending this drug for treat-ment of canine PF.

Recently, a small pilot study evaluating the efficacy oforal cyclosporin (5–10 mg kg−1 once daily) in five dogs withPF was reported.72 Four dogs did not complete the trialbecause of perceived lack of efficacy. In one dog, there wasa transient reduction in lesional scores.72 Future studiesshould evaluate whether this drug could be used as aglucocorticoid-sparing agent, or whether higher dosagesare needed to induce lesion remission.

The treatment outcome of canine PF appears to bevariable, presumably because of variations in treatmentprotocols and/or disease subtypes. In articles describingcases seen in the 1970s and 1980s, 18 of 34 (53%)5 and23 of 26 (88%) dogs with PF6 were reported to have been‘managed successfully’ with the interventions mentionedabove.

More recently, 43 dogs with PF were seen at the Uni-versity of Pennsylvania between 1994 and 2000.73 Of thesepatients, only 17 of 43 subjects (40%) were still alive at theend of the study period. Most dogs died during the firstyear of treatment. Of the dogs that died, 18 of 26 (69%)were euthanized because of lack of response of lesions totherapy, poor quality of life or adverse effects of treat-ment.73 Interestingly, the addition of antibiotics during theinduction of immunosuppression was associated with asignificant improvement in survival rate in this cohort ofpatients.73

In contrast to such results that suggest a poor outcomefollowing ‘standard-of-care’ therapy with combined oralimmunosuppression, Rosenkrantz reported a 71% survivalrate after one year in 31 dogs with PF with only four dogseuthanized because of poor response to therapy or treat-ment discontinuation with subsequent relapses.69 Similarly,the latest series of 91 dogs with PF reported by Muellerand colleagues provided additional data on favourabletreatment outcome.7 Of 88 dogs treated for PF, 46 under-went complete remission (52%), 31 (35%) achievedpartial remission of lesions, and only 11 (13%) were euth-anized.7 Reasons for euthanasia included lack of responseto treatment (4/11; 36%), unacceptable side-effects ofmedications used (2/11; 18%) and unrelated or unknowncauses.7 Complete remission was achieved with oral glu-cocorticoids in 15 of 39 dogs (38%) within 1.5–12 monthsof treatment initiation (average: 7 months), and this occurredwith a glucocorticoid–azathioprine combination in 18 of 33dogs (55%) within 2–29 months (average: 12 months) ofstarting therapy. Therefore, the addition of azathioprine didnot lead to a significant difference in the time needed toachieve remission compared to the use of glucocorticoidsalone.7 In five dogs, however, the sole administration ofprednisolone was unsuccessful, and the addition of azathi-oprine led to complete lesion remission.7 Remarkably,adverse drug events occurred significantly more often withprednisolone–azathioprine combination than glucocorticoidsalone. These observations suggest that a prospectivestudy must be undertaken to determine whether or notthe addition of azathioprine offers any benefit to glucocor-ticoid monotherapy in dogs with PF.

In this series of dogs with PF, there were no significantdifferences in either rate of complete remission or deathbetween dogs with facial localized vs. generalized lesions,dogs treated with prednisolone alone vs. prednisolone andazathioprine combination, or dogs treated with immuno-suppression with or without antibiotics.7 In summary, thereview of treatment outcome in this cohort of dogs withPF suggests that the benefit of azathioprine addition tooral glucocorticoid regimens must be weighed carefullyagainst the cost of treatment monitoring and additionalrisk to patients.

Finally, the persistence of long-term remission of caninePF after discontinuation of immunomodulating therapyhas been reported in 7–22% of dogs with PF.31 Similarresults were obtained in two of 88 dogs (2%) in the mostrecent case series. 7

In cats with PF, glucocorticoid monotherapy usually iseffective for achieving clinical remission. Historically, theoral glucocorticoids of choice have been prednisone (4–5 mg kg−1 daily) and triamcinolone (0.6–2 mg kg−1 daily).9

Figure 20. Canine PF. The intradermal injection of IgG from dogs with PF into neonatal mouse skin results in subgranular blister formation, thereby confirming the pathogenicity of serum autoantibodies (haematoxylin and eosin).68


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Recent pharmacological data, however, have shown thatoral prednisone is not very well absorbed and/or con-verted into prednisolone in cats, therefore suggesting thatoral prednisolone is a better choice than prednisone in thisspecies.74 In cats whose PF lesions fail to respond to glu-cocorticoids, chlorambucil (0.2 mg kg−1, orally, once daily)is the cytotoxic drug most commonly used.9,75 Even thoughazathioprine has been used successfully to treat cats withPF40 this drug is no longer used widely as it is known tocause profound neutropenia and thrombocytopenia infeline patients.76 This abnormal sensitivity to azathioprinemay be due to their recently discovered lower activity ofthiopurine methyltransferase, an enzyme that metabolizesazathioprine and whose deficiency can cause severemyelosuppression.77,78 Sometimes, lesions of feline PFrespond to aurothioglucose.6

In one study, complete remission of PF lesions occurredin 15 of 15 cats (100%) using triamcinolone alone, in eightof 13 (62%) using prednisone alone, and in nine of 11(82%) using a prednisone/chlorambucil combination.9 Inthat series of cases, cats receiving triamcinolone exhibiteda higher rate of complete remission and a lower rate ofadverse drug events than those receiving a prednisone/chlorambucil combination.9 Only four of 30 cats (13%) forwhich long-term treatment outcome was known wereeuthanized because of their disease or to treatment com-plications.9 In an older series of 10 cats with PF, treatmentwith prednisolone was reported to be effective in six subjects(60%) and with aurothioglucose in four patients (40%).6

Similarly to dogs and cats with this disease, lesions ofPF can be treated successfully in horses and goats witheither prednisolone or dexamethasone alone or in combi-nation with aurothioglucose.6,12,15 As is seen in cats, pred-nisone may be of limited efficacy in horses due to its poorabsorption and/or biotransformation into prednisolone.79

In one of the retrospective studies, five of 13 horses(38%) were euthanized for either lack of response oflesions to treatment or development of steroid-inducedacute laminitis.12 Four of 11 horses (36%) remained inremission for more than one year after immunosuppres-sion lasting from three to 12 months was discontinued.12

In the second study, follow-up information was reportedfor seven of 15 horses.11 Only one subject was euthanizeddue to financial constraints, while the other horses achievedremission with prednisone, prednisolone or aurothioglu-cose.11 In one horse, long-term remission was maintainedin the absence of treatment.11 Of note is that none of thethree published case series provided information substan-tiating the previously held belief that equine PF is of betterprognosis in young horses than in old subjects.

Conclusions: diagnosing pemphigus foliaceus in

domestic animals

In summary, at the time of this writing (June 2006), it isapparent that canine PF appears to be clinically, histologi-cally and immunologically heterogeneous with only rarepatients having autoantibodies targeting dsg1, the caninehomologue of the major human PF antigen. It is likelytherefore that the entity currently called ‘canine PF’ maynot be a single disease, but a clinicopathological syndromeregrouping several immunological variants. In many ways,this situation is similar to the recent reclassification of

human cicatricial pemphigoid within the spectrum of‘mucous membrane pemphigoid’.80 Whether feline, equineand caprine PF are immunologically heterogeneous cur-rently remains unknown.

As a result, and until further studies allow a refinementin the nosology of this syndrome, we propose that thediagnosis of PF be based principally on clinico-pathologicalgrounds. Therefore, it is suggested that, at this time, thediagnosis of PF be given to animals that suffer from a skindisease satisfying ALL three criteria below:

1 Clinical examination: pustules rapidly evolving inshallow erosions and crusts with predominance tothe face and feet

2 Histopathology: superficial epidermal or follicularpustules rich in neutrophils and often-clusteredacantholytic keratinocytes

3 Differential diagnoses: rule out of other acantholyticneutrophilic pustular diseases, especially exfoliatin-associated staphylococcal pyodermas and pustulardermatophytosis due to corneophilic dermatophytes.

Pemphigus erythematosus

In humans, PE is a controversial clinically heterogeneousentity that has been historically linked to both discoidlupus erythematosus (DLE) and superficial pemphigus.81

Supporting the current concept that human PE in fact rep-resents a variant of PF, immunological investigations haveconfirmed the identity of the main human PE autoantigenas dsg1, the major PF antigen.82,83 Additionally, serumautoantibodies targeting the basement membrane zoneantigens bullous pemphigoid antigen 1 (230 kDa) and peri-plakin (190 kDa) have been identified in rare patients.83

The first mention of the existence of PE in animals wasin a general review article of immunological skin diseasesby Scott in 1978.84 Two years later, the same author includedpreviously reported cases in an article describing clinical,histopathological and immunological characteristics offour dogs and one cat with PE.85 In June 2006, the searchof several reference databases identified – in addition tothe original princeps descriptions – only one case series ofnine dogs6 and scattered case reports of canine39,86–90

and feline PE.91

In the largest case series, PE was reported to be thethird most common form of pemphigus seen at CornellUniversity Veterinary Teaching Hospital, yet patients withPE only accounted for less than one of 1000 dogs and catspresented with skin diseases over 10 years.6 Unfortunately,due to the scarcity of information on canine and feline PE,detailed information on any breed, age and sex predispo-sition for this disease cannot be provided.

Clinically, dogs and cats with PE are reported to presentwith pustules erosions and crusts localized to the faceand pinnae along with depigmentation, erythema anderosion/ulceration of the nasal planum and dorsal muzzle(Fig. 21).6,39,85–91 Only rare patients exhibit nonfacial lesions.6

Microscopic examination of skin biopsies of dogs and catswith PE reveals intragranular to subcorneal neutrophilicand eosinophilic acantholytic pustules suggestive of PFalong with a lichenoid interface dermatitis that resemblesthat of DLE.6,39,85–91



On direct IF examination, skin biopsy specimens ofcanine and feline PE uniquely exhibit both intercellularepidermal pemphigus-like and basement membranelupus-like depositions of immunoglobulins with or withoutactivated complement.6 Of note is that not all dogs withPE will have this basement membrane immunoreagentdeposition.6,85 Indirect IF performed with canine and felinePE sera has remained negative for all patients tested.6,85

In contrast, low serum titres of antinuclear antibodies(1 : 10–1 : 40) have been identified in approximately halfof sera from dogs with PE.6,85

The treatment outcome of canine and feline PE isreported to be good, with lesions responding to immuno-suppressive regimens used to treat patients with PF.6 Inone of two dogs with PE, the administration of a tetracyclineand niacinamide regimen resulted in a partial resolution ofclinical signs.70 The use of sun avoidance and sunscreenshas been advocated.6 Finally, topical treatment with 0.1%tacrolimus ointment was reported to be of benefit, as anadjunct medication, in two dogs with PE.89

In summary, the rare descriptions of canine and felinePE published since 1980 have implied that this diseaserepresented an unusual facial-predominant dermatosis withclinical, histopathological and immunopathological charac-teristics of both PF and DLE. As a result, the current dogmais that PE might be a crossover between these two entities.

This concept must be considered controversial, how-ever. Indeed, the rationale for previous individualizationof canine PE as an entity distinct from PF needs to be re-examined in light of recent knowledge suggesting thatboth diseases exhibit very similar characteristics:

1 The predominance of skin lesions to the face is notunique to PE, as facial lesions are identified also inmost dogs with PF, and they are restricted to this areain 16% of canine patients with this disease.7

2 Photosensitivity is not specific for canine PE, as pre-liminary evidence suggests that this phenomenonexists also for canine PF (see discussion in the PFsection).

3 Superficial acantholytic epidermal pustules are seenin both canine PF and PE, while the presence of alichenoid ± interface dermatitis in the latter may onlyreflect the nasal/paranasal location of skin biopsies indogs with PE. Indeed, dogs with various nasal derm-atoses often exhibit a band-like diffuse superficialplasmacytic to lymphoplasmacytic dermatitis with orwithout basal cell damage.92

4 The observation of immunoglobulins and complementat the basement membrane zone by direct IF is notspecific for lupus, as it is seen also in canine PF andnumerous other immune-mediated skin diseases.53,93

Moreover, serum antibasement membrane autoanti-bodies can be detected in some dogs with PF.58

5 The presence of low serum titres of antinuclear anti-bodies in dogs with PE is not unique to this entitybecause of the recent observation that nearly 30% ofdogs with various phenotypes of PF also exhibit lowtitres of serum IgG targeting nuclear antigens.58

6 Finally, PE cannot be individualized from PF on thebasis of differing treatment outcomes as a favourableresponse to treatment is seen both in dogs with PE andin canine patients with localized or generalized PF.7

In summary, at this time, there is insufficient evidencesupporting that canine PE is markedly different from local-ized facial PF either clinically, histologically, immunologi-cally or prognostically. Additional studies are needed todetermine whether there would be any value – for eitherpatients or clinicians – in individualizing canine PE as aseparate entity, whether it should be reclassified as alocalized variant of PF, or whether it is a genuine crossoverbetween PF and DLE or other entities. Similarly, there isnot enough information on feline PE and PF to permit anaccurate separation between these two diseases.

Panepidermal pustular pemphigus

In 1994, Wurm, Mattise and Dunstan proposed the crea-tion of a new entity named ‘canine panepidermal pustular

Figure 21. canine ‘PE’. A 2-year-old collie presented with a pustular, erosive and crusting dermatosis bilaterally and symmetrically distributed to the face (left) and ears. Additionally, there were depigmenting atrophic scars, erosions and crusts on the dorsal nasal planum (right, top) as well as depigmentation, scarring and deep erosions/ulcers on the ventral nares (right, middle and bottom). Histological and immunological characteristics resembled those previously reported for canine PE.


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pemphigus’ to regroup cases previously diagnosed aspemphigus vegetans and PE.94 The main criteria for diag-nosing canine PPP were the demonstration of neutrophil-rich and eosinophil-rich acantholytic pustules at all layersof the epidermis and the suprabasal infundibular outer rootsheath epithelium.94 A considerable morphologic overlapbetween PPP and PF in dogs was noted to exist, but themain difference between these two entities was theobservation of pustules in the granular and upper spinouslayers in PF and the occurrence of these lesions through-out the epidermis in PPP.94

The rationale for creating an entity solely based onhistological grounds is subject to controversy. Indeed, asnoted above, there is current evidence of clinical, his-topathological and immunological heterogeneity amongdogs diagnosed with PF, and the individualization of distinctsubsets of canine pemphigus must await the determina-tion whether the identification of the various autoantigenstargeted provides a rationale for a revision of disease clas-sification. Indeed, the observation of microscopic lesionsarising at different epithelial depth simply could be due tovariability in distribution of antigens targeted by autoanti-bodies at different body locations. This concept is bestillustrated by the recent discovery that, for example, dsg1can be detected on keratinocytes of all epidermal layers inthe dorsal muzzle, pinna and footpads of dogs.95 In contrast,dsg1 is visible only in the upper layers of canine shoulder,groin or abdomen epidermis.95 Therefore, dogs with antidsg1associated pemphigus would be more likely to exhibitsuperficial lesions on the abdomen and groin and more‘panepidermal’ lesions on the muzzle, ears and footpads.

In summary, at the time of this writing, there is littleevidence supporting the separation of canine PPP from themain superficial pemphigus group (e.g. PF). Further studiesare needed to determine whether clinical, treatmentoutcome and immunological information warrants theindividualization of PPP as a bona fide entity.

Conclusions

The last decades have seen the discovery of canine, feline,equine and caprine homologues of superficial pemphigusin humans. The 1980s and early 1990s saw the separationof several subtypes of pemphigus (PF, PE and PPP)because of minor differences in gross and microscopiclesions. However, the recent observation of clinical, histo-logical or immunological overlap between these threeentities and the discovery of marked heterogeneity amongdogs with PF suggests that, until further investigationshave characterized the major autoantigens in this group ofdiseases, there is not enough evidence to warrant individ-ualizing subsets within the superficial pemphigus group inanimals. The terminology of ‘PF’ remains most appropriateat this time, keeping in mind that this denomination mightrepresent a syndrome rather than a homogeneous entity.

Acknowledgements and funding

The author is grateful to Drs Gregg Dean, Luis Diaz, ToshirohIwasaki, Eliane Mueller, Koji Nishifuji, Maja Suter, SimonWarren and Zhi Liu for their past and current collaborationsin the field of canine pemphigus foliaceus research. Twelve

years of continuous technical support by Stan Dunstonalso is acknowledged.

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Résumé Chez l’homme, la dénomination pemphigus regroupe un ensemble de dermatoses autoimmunes caractériséespar une séparation intraépidermique résultant d’un détachement cellulaire par acantholyse. Ces entités sont classées ense basant sur la profondeur du clivage épidermique, et des formes superficielles (pemphigus foliacé, pemphigus à IgA) etdes formes profondes (pemphigus vulgaire, pemphigus vegetant et pemphigus paranéoplasique) sont décrites. Chez lesanimaux domestiques, des formes de pemphigus ont été rapportées depuis le milieu des années 70 et la classificationanimale ressemble à celle utilisée chez l’homme. Cet article décrit les données récentes sur l’épidémiologie, les signescliniques, l’histopathologie, l’immunopathologie et le traitement des pemphigus superficiels chez les animaux domes-tiques. Des données détaillées sur le pemphigus foliacé canin, félin, équin et caprin, sur le pemphigus érythémateux caninet félin et sur le pemphigus panépidermique pustuleux canin sont présentées.

Resumen En humanos la denominación pénfigo engloba un grupo de enfermedades vesiculares de la piel con sepa-ración intraepidermal resultando en desunión intercelular y acantolisis. Las entidades se clasifican en base al nivel de for-mación de vesículas en la epidermis, y tanto variantes superficiales (pénfigo foliáceo, pénfigo con deposición de IgA) comoprofundas (pénfigo vulgar, pénfigo vegetativo y pénfigo paraneoplástico) son reconocidas. En animales domésticos,variantes de pénfigo han sido reconocidas desde la mitad de la década de 1970, y la clasificación de las enfermedades seasemeja a la utilizada en seres humanos. Este artículo revisa el conocimiento actual sobre la epidemiología, signos clínicos,

http://www.emedicine.com/DERM/topic317.htm



histopatología, inmunopatología y resultados del tratamiento de las variantes de pénfigo superficial en animales domésticos.Se ofrece asímismo una información detallada sobre pénfigo foliáceo en perros, gatos, caballos y cabras, pénfigo eritematosoen perros y gatos, y pénfigo pustuloso panepidermal en perros.

Zusammenfassung Beim Menschen umfasst die Pemphigus-Bezeichnung eine Gruppe von autoimmunen blasen-bildenden Hauterkrankungen mit intraepidermaler Separation, welche aus einer Zell-Zell Loslösung durch Akantholyseresultiert. Die Gruppen werden nach dem Ausmaß der Blasenbildung in der Epidermis eingeteilt, wobei sowohl oberflächliche(Pemphigus foliaceus, IgA Pemphigus) als auch tiefe (Pemphigus vulgaris, Pemphigus vegetans und paraneoplastischerPemphigus) Varianten anerkannt sind. Bei Haustieren sind Untergruppen von Pemphigus seit der Mitte der 1970er Jahrebekannt, und die Klassifizierung der Erkrankung ist jener ähnlich, die für humane Patienten verwendet wird. Dieser Artikelüberarbeitet das neueste Wissen in bezug auf Epidemiologie, klinische Symptome, Histopathologie, Immunpathologie undBehandlungserfolge von oberflächlichem Pemphigus bei Haustieren. Detaillierte Informationen über Pemphigus foliaceusbeim Hund, bei der Katze, beim Pferd und bei der Ziege, über Pemphigus erythematosus beim Hund und bei der Katze,sowie über den panepidermalen pustulösen Pemphigus beim Hund werden geliefert.

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