Clinical, Histopathological and Immunological Characteristics of Exfoliative Cutaneous Lupus Erythematosus in 25 German Short-haired Pointers

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2005 European Society of Veterinary Dermatology 239

Veterinary Dermatology 2005, 16 , 239252

BlackwellPublishing,Ltd.

Clinical, histopathological and immunological characteristicsof exfoliative cutaneous lupus erythematosus in 25 German

short-haired pointersSHARON L. BRYDEN*, STEPHEN D. WHITE, STANLEY M. DUNSTON,

AMANDA K. BURROWS* and THIERRY OLIVRY

*Murdoch University Veterinary Hospital, Division of Health Sciences, School of Veterinary and BiomedicalScience, Murdoch University, Murdoch, Western Australia 6150, Australia

Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh,North CA 27606, USA

Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California, Davis,CA 95616, USA

(

Received

14 October

2004; accepted

15 June

2005)

Abstract

Clinical, histopathological and immunological features of exfoliative cutaneous lupus erythematosus,an uncommon generalized exfoliative dermatitis occurring exclusively in German short-haired pointers, werecharacterized in 25 dogs. The disease affects young adult dogs and its familial incidence strongly suggests a hered-itary origin. Lesions were characterized by scaling and alopecia affecting 100 (25/25) and 76% (19/25) of dogs,respectively. Follicular casts were present in 28% (7/25) of dogs. The muzzle, pinnae and dorsum were typicallyaffected. Generalized skin lesions were described in 52% (13/25) of dogs. Systemic signs of pain and lamenessaffected several dogs. Anaemia and thrombocytopenia were detected in several dogs with a more severe clinicalphenotype. The most common histopathological features were hyperkeratosis and a lymphocytic interface der-matitis. Direct immunostaining revealed IgG deposition in the epidermal and follicular basement membrane of 100 (19/19) and 41% (7/17) of dogs, respectively. Circulating antifollicular and antisebaceous gland IgG anti-bodies were demonstrated by indirect immunostaining in 57% (4 /7) of dogs. This disease usually responds poorlyto immunosuppressive therapy and it has a guarded prognosis. Where outcome was recorded, 85% (10/12) of dogs were euthanased due to either a failure to respond to, or complications associated with, immunomodulatorytherapy. Two affected dogs are in remission and maintained on immunomodulatory dosages of prednisolone. This

study demonstrates the existence of a cellular and humoral immune response directed against the epidermalbasement membrane of dogs with exfoliative cutaneous lupus erythematosus. Additional studies are required to

further characterize the immunological pathogenesis of this disease.

INTRODUCTION

An acquired, generalized exfoliative dermatitis origi-nally reported as hereditary lupoid dermatosis of theGerman short-haired pointer (GSP)

1

has been described

as unique to this breed. It has previously been reportedin European, American and Australian GSP dogs.

17

Dogs clinically affected with this skin disease arereportedly young adults between 6 months and 2.75 yearsat the age of onset.

16

These dogs develop scaling thatinitially affects the face, pinnae and dorsum and whichprogresses to a more generalized distribution.

17

Peripheral lymphadenopathy and, less often, pyrexiahave been reported.

17

As affected subjects exhibit alymphocytic interface dermatitis similar to lupus-specicdermatoses of humans, it has recently been proposed

to call this syndrome exfoliative cutaneous lupuserythematosus (ECLE) of GSP.

2

The pathogenesis of ECLE is poorly understood butthe recognition of this disease exclusively in GSP andits familial incidence strongly suggest a hereditary

origin.

1,6

Histological examination of skin biopsyspecimens from affected dogs reportedly reveals alymphocyte-rich interface dermatitis and supercialmural folliculitis as the dominant histopathologicalpattern.

2

IgG has been detected by direct immunouo-rescent testing at the epidermal and infundibular basementmembrane in the majority of dogs evaluated.

2

Circulatingbasement membrane or sebaceous gland-specic auto-antibodies or antinuclear antibodies, however, havenot been detected previously in affected dogs.

2

Successful management of ECLE has proven frus-trating with a lack of consistent response to individualtherapies.

27

Topical antiseborrhoeic shampoo andhumectant application, oral fatty acid supplementationand oral tetracycline and niacinamide administrationhave all produced transient improvement but have failedto achieve long-term remission.

27

Immunosuppressive

Correspondence: Sharon Bryden, Murdoch University VeterinaryHospital, Division of Health Sciences, School of Veterinary andBiomedical Science, Murdoch University, Murdoch, WesternAustralia 6150, Australia. E-mail: [email protected]


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therapy using prednisolone has been used successfullyto treat ECLE in three GSP siblings, in combinationwith azathioprine in one dog

6

The prognosis for thisdisease is poor because of a failure to respond to, orcomplications associated with treatment.

27

In this study we sought to dene further the genetic

background and clinical features, as well as the manage-ment and prognosis, of dogs with ECLE by detailedretrospective evaluation of available case records.Pedigree information, where available, was accessedeither from the medical records or from owners of theaffected dogs. Interpretation of the pedigree data wascompleted by one of the authors (SW). In addition, thehistopathological and immunological features of ECLEwere further studied by obtaining archived parafn-embedded skin biopsy specimens and stored frozenserum samples from affected individuals and perform-ing histological and direct and indirect immunouo-rescence and immunohistochemical studies on allavailable material. These studies were completed by theauthors (SB and TO) at North Carolina State Univer-sity, North Carolina.

MATERIALS AND METHODS

Case material

Case material was included from 25 GSP dogs fromveterinary private practices and referral institutions inthe USA, UK and Australia in which a clinical andhistopathological diagnosis of ECLE had been made by

the referring veterinarian. A retrospective evaluationof the patient records (seven dogs) or a questionnairecompleted by the referring veterinarian (18 dogs) wasused to collect information on the history and clinicalsigns from all 25 dogs, and treatment from 23 dogs.Long-term follow-up was available for 13 dogs. Pedi-gree information was available for 15 of the 25 dogs(see Table 1). In addition, pedigree information wasincluded from another four affected dogs not includedin this study.

Histological examination

Skin biopsy material was available for 23 dogs (seeTable 1). Routinely processed, parafn-embedded blockswere sectioned and stained with haematoxylin & eosin.Histological features of hyperkeratosis, interface der-matitis (dened as basal vacuolation, blurring of base-ment membrane zone and basal apoptosis), apoptosiswithin the upper epidermis, lymphocytic inltration of the upper and lower epidermis and supercial dermis,interface mural folliculitis and sebaceous gland andsweat gland inammatory inltrate were evaluated.Microscopic features of each section were scoredsemiquantitatively as follows: intensity absent (0), mild(1), moderate (2) or marked (3) and extent absent (0),focal (1), multifocal (2) or diffuse (3). The average scorefor each dog was then calculated for each parameter.The number of dogs with a score fullling the criteria forabsent (0), mild (0.011), moderate (1.012) or marked

(2.013) was then calculated (see Table 4). The absenceof sebaceous glands was also recorded for each section.

Skin biopsy specimens were available from 23 dogs,with one dog (case 10) sampled twice at an interval of 3 months. Ninety-nine sections were evaluated in total.

Direct immunouorescence

In situ

deposition of IgG, IgA and IgM antibodies andactivated complement (C3 component) was detectedby direct immunouorescence (IF) testing of parafn-embedded sections from 19 dogs (see Table 1).

These were deparafnized, rehydrated and digestedwith 0.1% trypsin (#T-8128, Sigma Chemical Com-pany, St Louis, MO, USA) for 35 min at 37

C for anti-

gen retrieval. After proteolysis, the sections were rinsedin phosphate buffered saline (PBS) and blocked with1% newborn calf serum (#N-4762, Sigma ChemicalCompany). The sections were incubated for 30 min atroom temperature with either goat antidog IgA (Fitc)(A40104F Bethyl Laboratories, Montgomery, TX,USA), goat antidog IgM (Fitc) (#A40116F BethylLaboratories), goat antidog C3 (Bethyl Laboratories)at 1 : 40 or rabbit antidog IgG (Fitc) (#672081 ICNBiomedical, Aurora, OH, USA) at 1 : 60. PBS replace-ment of antibody and normal canine spleen served asnegative and positive controls, respectively. After fur-ther rinsing with PBS the sections were counterstainedwith Evans Blue (#E013, Sigma Chemical Company),2 drops per 500 mLs for 10 s and mounted withVectashield DAPI (#H 1200, Vector Laboratories,Burlingame, CA, USA).

Table 1. Case material and investigations performed

Case # Q/ MR Pedigree Histo DIF IIF IHC Follow-up

1 Q + + + + + +2 Q + + NT NT + NT3 Q + + NT NT + NT4 Q + + + NT + +

5 Q + + + NT + NT6 Q + + + NT + +7 Q + + + NT + +8 Q + + + NT NT NT9 Q + + + NT + NT10 Q + + + NT + +11 Q + + + NT + NT12 Q + + + + + NT13 Q + + + + + +14 Q NT + + NT + NT15 Q NT + NT NT + +16 Q NT + NT NT + +17 Q NT + + NT + NT18 Q NT + + NT + NT19 MR NT + NT + + +

20 MR NT + + + + +21 MR NT + NT + NT +22 MR NT + + NT NT NT23 MR + NT + NT + +24 MR + + + + + +25 MR NT NT + NT NT NT

Q Questionnaire; MR Medical Record; + Materialavailable for investigation; NT Investigation not performed;Histo Histopathology; DIF Direct Immunouorescence;IIF Indirect immunouorescence; IHC Immunohistochemistry.


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Characteristics of exfoliative cutaneous lupus erythematosus 241

Seventy-six biopsy specimens from 19 dogs wereevaluated using an epiuorescence microscope. Immuno-uorescence was recorded as either present or absent atthe basement membrane zone, sebaceous gland or hairfollicle level for each biopsy section. In addition, theextent of the uorescence as focal, multifocal or con-

tinuous and a qualitative assessment of either a ne orthick deposition were recorded.

Indirect immunouorescence

Detection of circulating basement membrane, hairfollicle or sebaceous gland specic autoantibodies wasachieved with an indirect immunouorescence methodusing normal canine intact lip, normal canine salt-splitlip and normal canine haired skin sections wasperformed in seven dogs (see Table 1).

8

These wereimmersed in acetone for 10 min and after rinsing inPBS were blocked with 1% newborn calf serum (#N-4762, Sigma Chemical Company) for 30 min in a moistchamber. The newborn calf serum was drained andeach patients serum was applied for 1 h at 1 : 10, 1 : 50and 1 : 100 dilutions at room temperature. For a nega-tive control, the patients serum was substituted withnormal canine serum (NCS#3) and PBS. For a positivecontrol serum from a dog with conrmed epidermoly-sis bullosa was utilized.

8

The sections were rinsed twicein PBS for 5 min then the secondary antibody, rabbitantidog IgG (#672081 ICN Biomedical, Aurora, OH,USA) was applied for 30 min in a moist chamber,followed by PBS rinse for 5 min. The sections werethen counterstained with Evans Blue (#E013, Sigma

Chemical Company) at 2 drops per 500 mL for 15 s.After nal rinsing, sections were mounted usingVectashield DAPI (#H 1200, Vector Laboratories).

Immunohistochemistry

Immunophenotyping of skin inltrating mononuclearcells was performed on unstained parafn-embeddedskin sections in 21 dogs using the T-lymphocyte markerCD3 to identify inltrating lymphocytes within theepidermis, dermis and pilosebaceous units (see Table 1).The sections were deparafnized and rehydrated for10 min and after rinsing in PBS were incubated with

3% protease (#P-5147, Sigma Chemical Company) for35 min at 37

C for antigen retrieval. After rinsing withPBS the sections were incubated with 1% newborn calf serum (NCS) (#N-4762, Sigma Chemical Company)for 20 min, then the primary antibody against CD3 at1 : 1000 was applied and incubated at room tempera-ture for 30 min. The sections were rinsed with PBS andthe secondary antibody goat antirabbit IgG (#1000,Vector Laboratories) at 1 : 400 was applied for 30 minat room temperature. After rinsing with PBS the tertiaryantibody Strepavidin-HRP (Zymed, San Francisco,CA, USA) at 1 : 400 was applied and incubated atroom temperature for 30 min. The sections were rinsedin PBS and AEC (Substrate Kit, Biogenex, San Ramon,CA, USA) applied, rinsed with water and counter-stainedwith haematoxylin. After nal rinsing the sections weremounted.

Lymphocytic inltrate was recorded for the upperand lower epidermis, supercial dermis, follicularinfundibulum, follicle below the level of the infundibu-lum, sebaceous and sweat glands. The extent of theinltrate was recorded as absent (0) focal (1), multi-focal (2) or diffuse (3) and the intensity as absent (0), mild

(1), moderate (2) or marked (3).

RESULTS

Case material

Twenty-ve dogs were affected with ECLE and of these17 were female and eight were male. The female to malesex ratio was approximately 2 : 1. Most of the dogswere from the USA (19), four were from Australia andtwo were from the UK. The median age of onset of ECLE was 10 months with a range of 1.848 months.

The most prominent skin lesions in the dogs werescaling and alopecia, which affected 25 (100%) and 19(76%) dogs, respectively (see Table 2 and Figs 14).Follicular casts were specically noted in seven (28%)dogs. Skin lesions typically affected the muzzle, pinnaeand dorsal trunk and then progressed to involve thelimbs and ventral trunk. Generalized skin lesions weredescribed in 13 (52%) dogs. Crusting, with or withoutassociated ulceration was recorded in six (24%) dogs.In one patient (case 19), ulceration was extensive andresulted in bacterial septicaemia. One dog (case 14)initially presented with depigmentation and ulcerationof the planum nasale (Fig. 2). Mild pruritus was recorded

in seven (28%) dogs.A generalized peripheral lymphadenomegaly

was reported in eight (32%) dogs. In seven (28%) dogs,intermittent episodes of pain (manifested as back arch-ing when standing, vocalizing, experiencing difcultiessitting or rising or displaying an altered gait) werereported by the owners. Three (12%) dogs experiencedintermittent pyrexia.

Laboratory evaluation

Serum biochemistry and haematological examinationwas performed on six and nine dogs, respectively (see

Table 2). A mild nonregenerative anaemia was recordedfor one dog (case 20) and an unspecied anaemia wasnoted in three others. Thrombocytopenia was recordedin six dogs. In four dogs there were no relevant bio-chemical abnormalities, one dog had a mild decrease inserum albumin, and another dog had a mild decreasein serum urea. Urinalysis was performed on one dog(case 19) and revealed mild proteinuria; however, theurine protein creatinine ratio was 0.4 units (normalrange < 0.5 units). Sera was obtained from eight dogsand evaluated for the presence of circulating anti-nuclear antibodies (ANA). In one dog (case 14) serumrevealed low levels of circulating antinuclear anti-bodies at a titre of 1 : 40. The sera of the remaining sevendogs were negative.

Fine-needle aspirate material from enlarged peripherallymph nodes was submitted for cytological evaluation


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Table 2. Clinical and laboratory results summary

CaseOnset(m) Country Sex Lesions Distribution

Concurrentclinical ndings Laboratory evaluation

1 10 USA F Scaling, alopecia pinnae and muzzle initially,then dorsum and hind limbs

NR CBC NSABiochemistry NSA

2 12 USA M Scaling, alopecia pinnae and muzzleand hind limbs

NR(demodicosis)

NR

3 6 USA F Scaling, alopecia,

follicular casts

generalized Lymphadenopathy,

pyrexia

CBC thromobocytope

lymphopenia, anaemia4 7 USA F Scaling, alopecia generalized Lymphadenopathy,pain/lameness

NR

5 3 USA F Scaling, alopecia,crusting andulceration

pinnae andmuzzle

Lymphadenopathy CBC thromobocytopenialymphopenia, anaemiaBiochemistrymild decrease in album

6 7 USA F Scaling generalized NR NR7 4 USA M Scaling, alopecia,

follicular castshead and dorsuminitially then hind limbs

NR NR

8 12 USA F Scaling, alopecia,follicular casts;mild pruritus

generalized NR NR

9 10 USA F Scaling, alopecia,crusting

muzzle NR NR

10 10 USA F Scaling, alopecia pinnae, muzzleand ventrum

pain/ lameness NR

11 14 USA M Scaling, alopecia,crusting, ulceration,erythema,mild pruritus

muzzle, pinnaeand dorsuminitially then ventrum

NR NR

12 14 USA F Scaling, alopecia,crusting, follicularcasts

muzzle, dorsum,ventrum andhind limbs

NR NR

13 9 USA F Scaling, alopecia,mild pruritus

generalized pain/ lameness NR

14 36 USA F Scaling, alopecia,erythema, mildpruritus, follicularcasts; ulcerationand depigment-ationof planum nasaleinitially

planum nasaleinitially;generalized

NR CBC mildthrombocytopenia,Biochemistry NSA

15 10 USA M Scaling, erythema generalized Lymphadenopathy NR16 1.8 USA M Scaling, alopecia generalized Lymphadenopathy

pain/lameness pyrexiaNR

17 42 USA F Scaling pinnae, planum nasale NR NR18 3 USA F Scaling, alopecia generalized Lymphadenopathy NR


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19 6 AUST M Scaling, alopecia,crusting, ulceration,follicular casts

muzzle and pinnae initiallythen dorsum, hind limbsbecoming generalized

Lymphadenopathy,pain/lameness,pyrexia, weightloss, demodicosis

CBC thrombocytopenBiochemistry NSA,UA proteinuria, UPC

20 8 AUST F Scaling, alopecia muzzle and dorsuminitially then pinnae

Lymphadenopathy CBC thrombocytopenia,anaemia (mildnonregenerative),Biochemistry mild

decrease urea21 10 AUST F Scaling dorsum initially then

pinnae and muzzleNR CBC NSA,

Biochemistry NSA22 6 AUST F Scaling, alopecia,

follicular castsdorsum Lymphopenia,

pain/lamenessCBC thromobocytopeanaemia

23 12 UK F Scaling, mildintermittent pruritus

dorsum initiallythen generalized scale

NR NR

24 4 UK F Scaling, moderateintermittent pruritus

pinnae, dorsum,muzzle then generalized

Pain/lamenessdemodicosis

CBC NSA

25 48 USA M Scaling, alopecia,mild intermittentpruritus

muzzle initiallythen generalized

Emaciated(abandoned)

NR

NR Not recorded; NRA No relevant abnormalities; UA urinalysis; UPC urine protein:creatinine ratio.

CaseOnset(m) Country Sex Lesions Distribution

Concurrentclinical ndings Laboratory evaluation

Table 2. Continued


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in one dog (case 20) with lymphadenomegaly andrevealed lymphoid hyperplasia. Spinal radiographs(cases 19, 20, 24), myelogram and cerebrospinal uid

(CSF) analysis (case 22) and stie and hock joint aspi-rates (case 19) were performed in dogs suffering fromintermittent pain but failed to identify any underlyingabnormality. Multiple deep skin scrapings identiedgeneralized demodicosis in three dogs receiving immu-nomodulatory therapy for ECLE.

Medical management

Information regarding medical management wasobtained retrospectively. In this light individual patientcase records often failed to specify the dose rate or theduration of prescribed treatments and the response totherapy. Most dogs received a combination of treat-ments including topical keratolytic and keratoplasticand/or antimicrobial shampoo therapies and emollientswith oral antimicrobial and immunomodulatory agents(see Table 3).

A number of immunomodulatory agents were pre-scribed either as single or combination therapy in all 23dogs and these included oral tetracycline (or doxycy-cline) with niacinamide (ve dogs), essential fatty acidsupplements (13 dogs), prednisolone (18 dogs), azathi-oprine (ve dogs), retinol and synthetic retinoids (threedogs), cyclosporin (one dog) and leunamide (onedog).

While there was no recorded response to therapy for16 dogs, the response to immunomodulatory therapyin the remaining nine dogs was, in general, poor.Temporary or partial remission was obtained in severaldogs using a combination of essential fatty acids andtetracycline (or doxycycline) and niacinamide butthe condition either relapsed (cases 7, 19) or failed toimprove (case 10). Similar responses were achievedwith the administration of oral retinol and retinoids(case 7). In one dog (case 1), signs partially respondedto leunamide with a reduction in pain but there was apersistence of dermatological signs. Pentoxifylline,cyclosporin, topical 0.015% triamcinolone spray (Gen-esis Virbac, AH, Fort Worth, TX, USA) and/or top-ical gentamicin and betamethasone spray (GentocinTopical Spray Schering AH, NSW, Australia) wereused to alleviate pruritus in two dogs (cases 11, 25).

Figure 1. Photo: case 14. Multifocal areas of alopecia over the

muzzle, trunk and hind limbs. Depigmentation is visible on theplanum nasale.

Figure 2. Photo: dorsal muzzle. Case 14. Alopecia and scaling onthe dorsal muzzle. Depigmentation is visible on the planum nasale.

Figure 3. Photo: Head. Case 19. Marked scaling and alopeciainvolving the muzzle, pinnae and head.

Figure 4. Photo: dorsal muzzle. Case 19. Marked scaling andalopecia involving the muzzle.


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Oral prednisolone was administered to 18 dogs and,where specied, dose rates ranged from 0.4 mg kg

1

to2 mg kg

1

orally every 24 h. In general, lower dosages

of prednisolone were not associated with clinicalimprovement whereas clinical remission was achievedwith higher dose rates in some cases. The most consistentresponse to immunomodulatory therapy was achievedwith three littermates (cases 19, 20 and 21) in whichremissions of 31, 20 and 24 months, respectively, wereachieved using oral prednisolone at 2 mg kg

1

q24 h incombination with topical keratolytic/keratoplasticand emollient therapy. The dog with the longest remis-sion (case 19) received concurrent azathioprine at2 mg kg

1

orally every 24 h.While there was no long-term outcome recorded for

12 dogs (see Table 1), 11 dogs were euthanased due toeither a failure to respond to, or complications associ-ated with, immunomodulatory therapy. One dog (case25) in this study is currently maintained on oral pre-dnisolone at a dosage of 0.25 mg kg

1

administered on

an alternate day basis in conjunction with oral essentialfatty acid supplementation. The referring veterinarianhas reported a waxing and waning of the disease course.

Pedigree information

Pedigree evaluation demonstrated that six dogs (seeTable 1) from the USA (cases 1, 2, 4, 6, 7 and 9) wererelated. In addition, four other dogs with ECLE (alsofrom the USA) not included in this study were relatedto these dogs. Figure 5 shows the familial relationshipof these 10 dogs. In addition, three other dogs (cases19, 20, 21) from Australia were full littermates. A fourthlittermate was not affected.

Histological examination

Histological examination of H&E-stained sections of skin biopsy specimens revealed a predominantly moder-ate, diffuse hyperkeratosis and moderate-to-marked,multifocal interface dermatitis in all dogs (see Table 4 andFig. 6). In addition, the majority of dogs demonstrated

Table 3. Treatment and Outcome Summary

Case Treatment Response Outcome

1 Topical, antibiotics (NR), prednisolone, leunamide Improvement after leunamide;marked reduction in pain butscaling and alopecia remained

Euthanased due to costof leunamide

2 NR NR; demodicosis NR

3 Antibiotics (cephalexin, enrooxacin), azathioprine NR NR4 Topical, antibiotics (NR), prednisolone, azathioprine NR Euthanased5 Topical, EFA, antibiotics (Clavamox) NR NR6 NR NR Euthanased7 EFA, tetracycline/niacinamide, antibiotics (NR), retinol 90% resolution within 1 month;

relapsed when withdrawnEuthanased

8 Topical, EFA, antibiotics (cephalexin), prednisolone NR NR9 EFA, antibiotics (cephalexin) NR NR10 Topical, tetracycline/niacinamide, prednisolone,

azathioprine, retinoids, pentoxifylline, zinc, vitamin Etemporary remission on retinoids andtopical, no response to prednisoloneazathioprine, tetracycline/niacinamide

Euthanased

11 Topical, EFA, prednisolone, retinol, topicalBetamethasone spray (Gentocin)

NR NR

12 Topical, EFA, antibiotics (cephalexin),prednisolone, azathioprine

NR NR

13 Topical, EFA, antibiotics (NR), prednisolone NR Euthanased after 4 years14 Topical, EFA, tetracycline/niacinamide,antibiotics (cephalexin), prednisolone

improved 1 month after commencingprednisolone, tetracycline/niacinamideand EFA

NR

15 Prednisolone NR euthanased16 Antibiotics (cephalexin), prednisolone NR euthanased17 Antibiotics (NR) NR NR18 Antibiotics (NR), prednisolone NR NR19 Topical, EFA, doxycycline/niacinamide,

antibiotics (cephalexin; enrooxacin and Clavulox whensepticaemic), prednisolone, azathioprine

Remission 31 m then waxing andwaning; demodicosis

Euthanased after 3.5 years

20 Topical, antibiotics (cephalexin, Clavulox) prednisolone Remission 20 m Euthanased after 2 years21 Topical, antibiotics (cephalexin), prednisolone Remission 24 m NR22 Topical, EFA, tetracycline/niacinamide,

antibiotics (Clavulox), prednisoloneNR NR

23 Topical, EFA, antibiotics (potentiatedsulphonamide), prednisolone

waxing, waning, EFA, topical currently,no response to low dose prednisolone

Currently treated

24 Topical, EFA, antibiotics (cephalexin), prednisolone NR; demodicosis Euthanased after 4 years25 Topical, EFA, antibiotics (cephalexin), prednisolone,

pentoxifylline, Genesis, antihistamine(diphenhydramine), cyclosporin

waxing and waning; concurrent atopy Currently treated

NR Not recorded; EFA essential fatty acids.


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mild, focal keratinocyte apoptosis and lym-phocytic exocytosis in the upper epidermis and a

moderate-to-marked, multifocal lymphocytic exocyto-sis in the lower epidermis. In addition, there wasmoderate-to-marked, multifocal supercial dermallymphocytic inltrate. A lymphocytic interface muralfolliculitis was present above the infundibulum in alldogs (where infundibula were present in the sections)and below the infundibulum in 92% (21/23) of dogs(Fig. 7). A lymphocytic sweat gland inltrate was seenin 46% (11/23) of dogs. Sebaceous glands were absentfrom all skin biopsies evaluated in four dogs and50% (25/50) of the total number of sections evaluated(Fig. 8). In sections with sebaceous glands, a mild,focal lymphocytic periglandular inltrate was presentin 63% (12/20) of dogs. In one dog (case 10) progres-sion of the disease over a 3-month period resulted incomplete absence of sebaceous glands from all skinbiopsy sections.

Direct immunouorescence (IF)

Direct IF testing performed on parafn-embedded

sections revealed the presence of in situ

deposition of IgG, IgM, IgA and C3 in the epidermal basementmembrane of 100% (19/19), 47% (9/19), 11% (2/19) and5% (1/19) of dogs, respectively (see Table 5). Multifo-cal, continuous, ne deposition of IgG was recordedin 61% (40/66), 35% (23/66) and 77% (50/66) of skinbiopsy sections, respectively (Fig. 9). IgG and IgM wasdetected in the follicular basement membrane of 41%(7/17) and 6% (1/17) of dogs, respectively (see Table 5).Deposition of IgA and C3 in the follicular basementmembrane was not observed. In situ

deposition of IgGand IgM was observed in the sebaceous gland basementmembrane of the sections from one dog only (case 17).

Indirect immunouorescence

Indirect IF testing on sections of normal canine haired-and salt-split-skin revealed the existence of circulating

Figure 5. Pedigree Chart. Key:Square = male; Circle = female;Red = affected (histologically conrmed);Numbered animals correspond to the dogsof this report listed in Tables 1, 2, 3 and 5.

Table 4. Histopathology Results

Hyperkeratosis Interface ApoptosisLymphocyticinltrate ued

Intensity Extent Intensity Extent Intensity Extent Intensity Extent

Absent (0) 0 0 0 0 7 7 4 4Mild/focal (0.11) 3 0 2 0 15 13 18 11Moderate/multifocal (1.012) 12 11 11 18 2 4 2 9Marked/diffuse (2.013) 9 3 11 6 0 0 0 0

Lymphocyticinltrate led

Lymphocyticinltrate sd

Interface aboveinfundibulum

Interface belowinfundibulum

Intensity Extent Intensity Extent Intensity Extent Intensity Extent

Absent (0) 0 0 0 0 0 0 2 2Mild/focal (0.11) 3 0 0 0 9 6 9 8Moderate/multifocal (1.012) 13 21 13 17 9 17 8 14Marked/diffuse (2.013) 8 3 11 7 5 0 5 0

Sebaceous

gland inltrate

Sweat gland

inltrateIntensity Extent Intensity Extent

Absent (0) 5 5 13 13Mild/focal (0.11) 13 12 10 7Moderate/multifocal (1.012) 2 2 1 4Marked/diffuse (2.013) 0 1 0 0

The number of dogs with an average histological score for each parameter. Intensity: absent (0), mild (0.011), moderate (1.012) and marked(2.013).Extent: absent (0), focal (0.011), multifocal (1.012) and diffuse (2.013). Ued = upper epidermis. Led = lower epidermis. Sd = supercial dermis.


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antifollicular IgG antibodies at the 1 : 100 dilution inthe serum of 57% (4 /7) of dogs (see Table 5 and Fig. 10).In addition, antisebaceous gland IgG antibodies werealso detected at 1 : 101 : 100 dilution in these dogs.Circulating antiepidermal basement membrane anti-bodies were not observed.

Immunohistochemistry

Immunohistochemical staining conrmed the predom-inance of CD3-bearing T lymphocytes in the lowerepidermis, supercial dermis, in the infundibulum of hair follicles and around sweat glands in 21 dogs (seeTable 5 and Fig. 11). CD3-positive T lymphocytes inl-trated sebaceous glands and associated ducts in samplescollected from two dogs (see Table 5 and Fig. 12).

DISCUSSION

This study conrms previously published reportsdening canine ECLE as a disease of young adult GSP.While previous reports did not show a sex predilection,it is interesting in this larger case series that the femaleto male ratio was approximately 2:1. Scaling and alopecia

are the most prominent clinical features. Lesions beginon the muzzle, pinnae and dorsum and typically progressto a generalized distribution.

17

Follicular casts havebeen reported previously

1,4

and were present in severalaffected dogs in this study. The casts represent anaccumulation of infundibulum stratum corneumadhering to the hair shaft above the surface of the

follicular ostia and occur as primary lesions in vitaminA responsive dermatoses, primary cornication defectsand sebaceous adenitis.

911

The presence of intermittent pain and lameness inseveral dogs in this study was a characteristic of ECLEnot consistently reported as a feature of the disease.

17

In this study, dogs with lameness or pain presentedwith a more severe phenotype of ECLE, with general-ized scaling and crusting, depression and pyrexia.Further diagnostic investigation including spinal radi-ographic evaluation, contrast myelogram, CSF analy-sis and multiple joint aspirates in a limited number of cases failed to identify any concurrent musculoskeletalabnormality. While a normal joint uid aspirate wouldeliminate the possibility of an active multiarticulararthritis in these dogs, other musculoskeletal abnor-malities including small joint arthralgia, myalgia,

Figure 6. Photomicrograph: canine epidermis. Lymphocyte-richinterface dermatitis and supercial mononuclear dermatitis. H&E.Bar = 35 m.

Figure 7. Photomicrograph: canine epidermis. Lymphocyte-richinterface mural (infundibular) folliculitis with keratinocyteapoptosis. H&E. Bar = 25 m.

Figure 8. Photomicrograph: canine epidermis. Absence ofsebaceous glands. H&E. Bar = 600 m.

Figure 9. Photomicrograph: canine epidermis. IgG autoantibodiesare deposited along the epidermal basement membrane zone(arrowheads). Direct immunouorescence, anticanine IgG-uorescein with DAPI counterstain. Bar = 25 m.


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myositis and tendonitis have been reported as an extra-cutaneous manifestation of systemic lupus erythema-tosus (SLE) in humans,

13,14

and could account for theundetectable source of pain in dogs with ECLE.

Haematological abnormalities of anaemia andthrombocytopenia were also detected, in general, in a

limited number of dogs in this study with a more severeclinical presentation of ECLE. Autoantibodies directedagainst erythrocytes and platelets lead to haemolyticanaemia and thrombocytopenia in canine SLE

13,14

butthe signicance of this nding in dogs with ECLE isunknown. With the exception of one dog (case 14),

Table 5. Immunological Testing Results

Case # DIF EBM DIF FBM DIF SBM IIF EBM IIF FOLL IIF SEB IHC

1 IgG, IgM neg 1 : 20 neg 1 : 20 neg 1 : 20 +2 NT NT NT NT NT NT +3 NT NT NT NT NT NT +4 IgG NT NT NT +

5 IgG NT NT NT +6 IgG NT NT NT +7 IgG, IgM NT NT NT +8 IgG IgG NT NT NT NT9 IgG NT NT NT +10 IgG NT NT NT +11 IgG NT NT NT +12 IgG neg 1 : 20 Neg 1 : 20 neg 1 : 20 +13 IgG, IgM neg 1 : 20 Neg 1 : 20 neg 1 : 20 +14 IgG IgG NT NT NT +15 NT NT NT NT NT NT +16 NT NT NT NT NT NT +17 IgG, IgM IgG, IgM IgG NT NT NT +18 IgG, IgM IgG NT NT NT +19 NT NT NT Neg 1 : 10 +1 : 100 +1 : 100 +

20 IgG, IgM Neg 1 : 10 +1 : 100 +1 : 50 +21 NT NT NT Neg 1 : 10 +1 : 100 +1 : 10 NT22 IgG, IgM NT NT NT NT23 IgG, IgM, IgA IgG NT NT NT +24 IgG, IgM, IgA, C3 IgG Neg 1 : 10 +1 : 100 +1 : 100 +25 IgG IgG NT NT NT NT

No deposition; NT Investigation not performed; DIF Direct Immunouorescence, EBM epidermal basement membrane,FBM follicular basement membrane, SBM sebaceous basement membrane; IIF Indirect Immunouorescence, FOLL Hair follicle, SEB

Sebaceous gland; IHC Immunohistochemistry CD3+ T lymphocytes.

Figure 10. Photomicrograph: canineepidermis. (a) Serum from a dog with ECLEcontains IgG that recognizes antigen(s)along the sebaceous gland basementmembrane (arrowhead). (b) Normal canineserum does contain such autoantibodies.Indirect immunouorescence using normalcanine haired skin, anticanine IgG-uorescein with DAPI counterstain.Bar = 20 m.


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none of the dogs in this study had circulating ANA,consistent with previous reports of ECLE.

2

It is welldocumented that ANA can be found in other caninediseases as well as in normal dogs and are therefore notspecic for SLE.

13,14

Microscopic examination of biopsy specimensfrom affected ECLE dogs demonstrated a lymphocyticinterface dermatitis and mural folliculitis with anabsence of sebaceous glands consistent with previouslypublished reports.

17,12

The histopathological ndings

are, however, not pathognomonic for ECLE. Otherdifferential diagnoses may include discoid lupuserythematosus (DLE), SLE, erythema multiforme (EM),vesicular cutaneous lupus erythematosus (VCLE) of the collie and Shetland sheepdog, and sebaceousadenitis.

1,12,15

Knowledge of the breed affected may be most help-ful in differentiating ECLE from VCLE given thestrong breed predilection for collies and Shetlandsheepdogs to be affected with this latter disease.

17,12,15

DLE lesions are usually restricted to the face and theprincipal histopathological nding is a more intenselichenoid interface band of dermal inammation andless marked hyperkeratosis than ECLE, although basalcell vacuolar degeneration and blurring of the base-ment zone could be similar in both diseases.

1,12

Clinically, the dermatological signs of canine SLEare pleomorphic but can present as a generalized ex-foliative dermatitis affecting the face, ears and distalextremities.

1,1214,16

The classic histopathological nd-ings of canine SLE are similar to canine DLE withmore severe basal cell vacuolation and apoptosis and aless intense lichenoid inammation of the dermis.The distinguishing histopathological features of ECLEcompared to classic SLE are the presence of moderateto marked hyperkeratosis and, in some cases, the absenceof sebaceous glands. In addition, a clinical diagnosis of

Figure 11. Photomicrograph: Canine Epidermis. T-lymphocytesinvade the lower epidermal layers. Immunohistochemistry CD3staining. Bar = 100 m.

Figure 12. Photomicrograph: canineEpidermis. T-lymphocytes invade sebaceousglands and sebaceous ducts.Immunohistochemistry CD3 staining.Bar = 150 m (inset: 100 m).


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SLE requires demonstration of multiple organ systeminvolvement with four of 11 criteria being satisedaccording to the classication system of the AmericanRheumatism Association.

14,16

Some cases of ECLE inthis study did present with concurrent haematologicaland musculoskeletal abnormalities. However, these

occurred in a limited number of dogs and, with theabsence of nonerosive arthritis and detectable serumANA, would not satisfy the inclusion criteria requiredfor a diagnosis of SLE.

The most characteristic histopathological feature of EM is the presence of apoptotic keratinocytes presentat all levels of the epidermis, accompanied by lym-phocyte satellitosis. 1,12 In ECLE, keratinocyte apopto-sis appears to be principally conned to the basal celllayers. However, individual necrosis of keratinocyteswas seen at all levels of the epidermis in approximately30% of sections, making it difcult to distinguishECLE from EM reliably using this criterion. Hyper-keratosis is not a feature of acute EM, and athoughhyperkeratosis may occur with chronic EM it is rarelymarked, in contrast with the ndings in ECLE. 1,12 EMis also typically negative on direct IF evaluation whereasimmunoglobulin deposition was identied at the base-ment membrane zone of all dogs with ECLE in thisstudy. Notwithstanding this, clinical differentiationmay be required: EM is characterized by an erythema-tous macular to papular eruption and it is uncommonfor the disease to occur in dogs of less than 1 year of age compared with ECLE where adolescent GSPdogs are affected with a predominantly exfoliative

dermatitis. 1,12,17Follicular casts or fronds associated with severe

adherent scaling and progressive alopecia are seen in apredominantly dorsal distribution of some breeds withsebaceous adenitis 1,1012 and bears some resemblanceto the clinical presentation of dogs with ECLE. Fur-thermore, the diffuse absence of sebaceous glands andunilateral peradnexal lymphocytic inammation in thesite of the sebaceous glands in dogs with ECLE doesresemble the histological lesions of sebaceous adenitis.An interface dermatitis and apoptosis are, however,principal histological features of ECLE and not typical

histological features of sebaceous adenitis.1,12

Any dis-ease involving primary or secondary destruction of sebaceous glands could result in scaling and the histo-logical absence of sebaceous glands thereby resemblingthe syndrome of sebaceous adenitis

The presence of an interface dermatitis in dogswith ECLE is suggestive of an underlying cytotoxicT-cell-mediated pathogenesis. Similarly the presence of CD3 bearing T lymphocytes in the epidermal, follicu-lar and sebaceous gland basement membranes suggestsa major histocompatibility complex (MHC) restrictedcell mediated immunological reaction to antigen(s)shared by these regions. Indirect immunostaining per-formed on normal and canine salt-split-skin revealed ahigh titre of circulating IgG specic against follicularbasement membranes and sebaceous glands in morethan half the dogs evaluated in this study. This is in

contrast with previously published reports where nocirculating autoantibodies against sebaceous glands orhair follicles were detected. 2 This, in combination withthe presence of xed tissue IgG antibodies present inthe epidermal basement membrane of all dogs inthis study, strongly suggests a combined cellular and

humoral immune response directed against basal cellsas the possible underlying pathogenetic mechanism inECLE. Inammation of the basement membrane mayresult in secondary destruction of sebaceous glandgerminative epithelium in the isthmus region, resultingin the generation of sebaceous gland and follicularautoantigens and the subsequent production of seba-ceous gland and follicular specic IgG autoantibodies.

In general, the response to immunomodulatorytherapy for dogs with ECLE was poor, with short- tomedium-term clinical remission achieved with a com-bination of topical keratolytic and keratoplastic sham-poo therapy and immunosuppressive treatment regimeswith prednisolone and/or azathioprine. More benignimmunomodulatory treatment combinations such asoral tetracycline and niacinamide, oral essential fattyacids and synthetic retinoids were not successful inachieving remission or were frequently associated withdisease relapse. The majority of dogs in this study,where a long-term or nal outcome was recorded, wereeuthanased either because of a failure to respond to, orcomplications associated with immunomodulatorytherapy.

While the pedigree data are limited in this study, theinformation available conrmed a shared ancestry in a

small number of affected dogs. The recognition of thisdisease in littermates also strongly suggests a here-ditary origin. The occurrence of ECLE in both male andfemale dogs, the uncommon nature of the disease andthe relatedness among some of the affected dogs ismost suggestive of an autosomal recessive mode of inheritance. However, a polygenic recessive mode(wherein the dog must inherit several alleles in order tohave the phenotype) cannot be ruled out. It must beemphasized that our data are very limited and pedigreeinformation from all affected individuals or breedingstudies would be required to conrm the exact mode of

inheritance.In conclusion, this study demonstrates that canineECLE is typically a disease of young adult GSP withan exfoliative dermatitis that presents variably withlameness and pyrexia. The disease responds poorly toimmunosuppressive therapy and has a guarded pro-gnosis. The classic histopathological features, althoughnot present in every affected dog, are a lymphocyticinterface dermatitis and mural folliculitis with secondaryloss of sebaceous glands. Furthermore, our ndingsreveal the existence of a cellular and humoral immuneresponse directed against the epidermal basementmembrane, hair follicles and sebaceous glands of dogswith ECLE. Additional studies are required to furthercharacterize the immunological pathogenesis of thisdisease, with particular reference to the temporal rela-tionship between the epidermal basement membrane


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and adnexal immune response and the pathogenicityand target of the antifollicular and antisebaceousgland antibodies.

ACKNOWLEDGEMENTS

The authors would like to thank the followingcolleagues for providing case information and/orhistological slides: G. Burton, A. Cannon, E. Codner,T. DeManuelle, G. Doering, R. Evans, K. Forstevedt,A. Foster, C. Friberg, D. Gold, T. L. Gross, L. Jonas,K. Kuhl, S. Shaw, M. Shipstone, S. Torres, C. Vitaleand C. Wraith. The authors would also like to thank R.C. Tryon for assistance with the pedigree chart, A.OHara for assistance with histopathology and J. Hoodfor invaluable advice with the manuscript.

REFERENCES

1. Gross TL, Ihrke PJ, Walder EJ. Hereditary lupoid der-matosis of the German Shorthaired Pointer. VeterinaryDermatopathology: a Macroscopic and MicroscopicEvaluation of Canine and Feline Skin Diseases. St Louis:Mosby Year Book, 1992: 268.

2. Olivry T, Luther PB, Dunston SM et al. Interface derma-titis and sebaceous adenitis in exfoliative cutaneouslupus erythematosus (Lupoid Dermatosis) of GermanShort-Haired Pointers. Proceedings of 15th AAVD/ACVD Meeting 1999: 412.

3. Theaker AJ, Rest JR. Lupoid dermatosis in a German

Short-haired pointer. Veterinary Record 1992; 21: 495.4. White SD, Gross TL. Hereditary Lupoid Dermatosis

of the German Shorthaired Pointer. In: Kirk RW,Bonagura JD. eds. Current Veterinary Therapy SmallAnimal Practice, Vol. XII. Philadelphia: W.B. SaundersCo., 1995: 6056.

5. Vroom MW, Theaker MJ, Rest JR et al. Lupoid derma-tosis in ve German short-haired pointers. VeterinaryDermatology 1995; 6: 93 8.

6. Bryden SL, Burrows AK. Successful management of

exfoliative cutaneous lupus erythematosus in threeGerman shorthaired pointer siblings. Veterinary Der-matology 2004; 14: 253.

7. Vercelli A, Schiavi S. A case report of lupoid dermatosisin a German short-haired pointer. Proceedings of the 3rdWorld Congress of Veterinary Dermatology 1996: 145.

8. Olivry T, Fine J-D, Dunston SM et al. Canine epidermo-lysis bullosa aquisita: circulating autoantibodies targetthe aminoterminal noncollagenous (NC1) domain of collagen VII in anchoring brils. Veterinary Dermatol-ogy 1998; 9: 1931.

9. Gross TL, Ihrke PJ, Walder EJ. Veterinary Dermatopa-thology: a Macroscopic and Microscopic Evaluation of Canine and Feline Skin Diseases. St Louis: Mosby YearBook, 1992: 94102.

10. Rosser EJ, Dunstan RW, Breen PT et al. Sebaceousadenitis with hyperkeratosis in the standard poodle: Adiscussion of 10 cases. Journal of the American AnimalHospital Association 1987; 23: 3415.

11. Reichler IM, Hauser B, Schiller I et al. Sebaceous

adenitis in the akita: clinical observations, histopathologyand heredity. Veterinary Dermatology 2001; 12: 243 53.

12. Yager JA, Wilcock BP. Colour Atlas and Text of SurgicalPathology of the Dog and Cat. Wolfe Publishing, 1994:906.

13. Chabanne L, Fournel C, Monier J-C et al. Canine Sys-temic Lupus Erythematosus Part I, Clinical and Biolog-ical Aspects. Compendium of Continuing Education forthe Practicing Veterinarian 1999; 21: 13541.

14. Chabanne L, Fournel C, Monier J-C et al. CanineSystemic Lupus Erythematosus Part II. Diagnosis andTreatment. Compendium of Continuing Education forthe Practicing Veterinarian 1999; 21: 40210.

15. Jackson HA, Olivry T. Ulcerative dermatosis of theShetland sheepdog and rough collie dog may represent anovel vesicular variant of cutaneous lupus erythe-matosus. Veterinary Dermatology 2001; 12: 1927.

16. Scott DW, Miller WH, Grifn CE. eds. Small AnimalDermatology, 6th edn. Philadelphia: W.B. Saunders,2001: 70117.

17. Scott DW, Miller WH, Grifn CE. eds. Small AnimalDermatology, 6th edn. Philadelphia: W.B. Saunders,2001: 72940.

Rsum Cette tude a caractris les donnes cliniques, histopathologiques et immunologiques de 25 cas delupus cutan exfoliatif, une dermatose exfoliative gnralise rare dcrite exclusivement chez les Braque allemands.La maladie atteint des chiens jeunes adultes, et son incidence familiale suggre une origine hrditaire. Les lsionssont caractrises par des squames et une alopcie affectant 100% (25/25) et 76% (19/25) des chiens respective-ment. Des manchons pilaires taient nots chez 28% (7/25) des chiens. Le chanfrein, les pavillons auriculaires etle dos taient typiquement atteints. Des lsions gnralises taient observes chez 52% (13/25) des chiens. Dessignes systmiques de douleur et de boiterie taient nots chez quelques chiens. Une anmie et une thrombocy-topnie taient dtectes chez quelques chiens, atteints dun phnotype svre. Les lsions histopathologiques lesplus frquentes taient une hyperkratose et une dermatite dinterface lymphocytaire. Limmunomarquage directa montr un dpt dIgG dans la membrane basale de lpiderme et des follicules pileux dans 100% (19/19) et41% (7/17) des cas respectivement. Des anticorps circulants antifolliculaires et anti glandes sbaces taientdmontrs par immunouorescence indirecte chez 57% (4/7) des chiens. Cette maladie rpond gnralementmal aux traitements immunosuppresseurs et est de mauvais pronostic. Lorsquun suivi a t dcrit, 85% (10/12)des chiens ont t euthanasis cause dune absence de rponse au traitement, ou aux complications de lathrapeutique immunosuppressive. Deux chiens atteints taient en rmission avec des doses immunosuppressivesde prednisolone. Cette tude dmontre lexistence dune rponse cellulaire et humorale dirige contre lamembrane basale chez les chiens lupus cutan exfoliatif. Des tudes supplmentaires sont ncessaires pourmieux caractriser la pathognie immunologique de cette maladie.


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Resumen En 25 perros se caracterizaron los procesos clnicos, histopatolgicos e inmunolgicos del lupuseritematoso cutneo exfoliativo, una rara dermatitis exfoliativa que ocurre exclusivamente en Pointers alemanesde pelo corto. La enfermedad afecta a jvenes adultos y su incidencia familiar sugiere claramente un origenhereditario. Las lesiones se caracterizaron por descamacin y alopecia, afectando a un 100% (25/25) y a un 76%(19/25) de los animales, respectivamente. Tambin se observaron cilindros foliculares en un 28% (7/25) de losperros. Las zonas tpicamente afectadas incluyeron el hocico, orejas y el dorso. Un 52% de los perros presentaronlesiones generalizadas (13/25). Varios perros se vieron afectados por signos sistmicos de dolor y cojera. Ademsen algunos perros se observ un fenotipo clnico ms severo con anemia y trombocitopenia. Las caractersticashistopatolgicas ms comunes fueron hiperqueratosis y dermatitis linfoctica de la interfase. Mediante tincininmunolgica directa observamos depsitos de inmunoglobulina G en las membranes basles de la epidermis yfolculos pilosos en un 100% (19/19) y un 41% (7/17) de los perros, respectivamente. Por otro lado, mediantetincin inmunolgica indirecta se detectaron anticuerpos circulantes del tipo IgG frente a las glndulas sebceasy folculos pilosos en un 57% (4/7) de los perros. La enfermedad generalmente presenta una respuesta inadecuadaa la terapia inmunosupresora y un pronstico grave. En los casos en los que se sigui la evolucin clnica, un 85%de los animales (10/12) fueron sacricados debido a la pobre respuesta al tratamiento inmunomodulador odebido a complicaciones derivadas del tratamiento. Dos de los perros afectados se encuentran actualmente enremisin y se mantienen con dosis inmunomoduladoras de prednisolona. Este estudio demuestra la existenciade una respuesta celular y humoral frente a la membrana basal de la epidermis en perros con lupus eritematosocutneo exfoliativo. Estudios complementarios seran necesarios para caracterizar la patognesis de laenfermedad.

Zusammenfassung Klinische, histopathologische und immunologische Charakteristika von exfoliativemkutanen Lupus erythematodes, einer seltenen generalisierten exfoliativen Dermatitis, die ausschliesslich beimDeutsch Kurzhaar Vorstehhund vorkommt, wurden bei 25 Hunden beschrieben. Diese Krankheit betrifft jungeadulte Hunde und das familire Auftreten ist ein starker Hinweis auf einen erblichen Ursprung. Die Lsionenwaren charakterisiert durch Schuppenbildung und Haarausfall, die bei 100% (25/25) bzw. 76% (19/25) der Hundeauftraten. Follikelkeratinmanschetten waren bei 28% (7/25) der Hunde vorhanden. Die Schnauze, die Ohrmuschelnund der Rcken waren typischerweise betroffen. Generalisierte Hautlsionen wurden bei 52% (13/25) derHunde beschrieben. Etliche Hunde zeigten systemische Zeichen von Schmerz und Lahmheit. Anmie undThrombozytopenie wurde bei mehreren Hunden mit ausgeprgterem klinischen Phnotyp gefunden. Thehugsten histopathologischen Befunde waren Hyperkeratose und eine lymphozytre Interface Dermatitis.Direkte Immunfrbung zeigte IgG Ablagerung in der epidermalen und follikulren Basalmembran von 100%(19/19) bzw. 41% (7/17) der Hunde. Zirkulierende IgG Antikrper, die gegen Haarfollikel und gegen Talgdrsengerichtet waren, wurden mit indirekter Immunfrbung bei 57% (4/7) der Hunde nachgewiesen. Diese Erkrankungreagiert im allgemeinen schlecht auf immunsupprimierende Therapie und hat eine vorsichtige Prognose. 85%(10/12) der Hunde, wo ein Endbericht vorlag, wurden euthanasiert entweder wegen fehlender Reaktion auf oderwegen Komplikationen mit immunmodulierender Therapie. Zwei betroffene Hunde benden sich in Remissionund werden mit immunmodulatorischen Dosen von Prednisolon dauerbehandelt. Diese Studie zeigt die Existenzeiner zellulren und humoralen Immunantwort, die gegen die epidermale Basalmembran bei Hunden mitexfoliativem kutanen Lupus erythematodes gerichtet ist. Zustzliche Studien sind notwendig, um dieImmunpathogenese dieser Krankheit weiter zu charakterisieren.

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Clinical, Histopathological and Immunological Characteristics of Exfoliative Cutaneous Lupus Erythematosus in 25 German Short-haired Pointers