A Retrospective Study Comparing the Histopathological Features and Response to Treatment in Two...

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© 2004 European Society of Veterinary Dermatology 341

Veterinary Dermatology 2004, 15, 341–348

BlackwellPublishing,Ltd.

A retrospective study comparing the histopathological featuresand response to treatment in two canine nasal dermatoses,

DLE and MCP

S. P. WIEME LT*, M. H. GOL DSCH MIDT†, J. S. GREEK‡, J. G. JEFFERS§,A. P. WIEMELT¶ and E. A. MAULDIN†

*Departments of Clinical Studies and †Pathobiology, University of Pennsylvania,

School of Veterinary Medicine Philadelphia, PA, USA

‡Veterinary Specialists of Kansas City, Overland Park, Kansas, USA

§Animal Dermatology Clinic, Rockville, Maryland, USA

¶Merck Research Laboratories, Merck & Co., Inc., West Point, PA, USA

(Received 4 April 2003; accepted 15 December 2003)

Abstract Canine discoid lupus erythematosus (DLE) and mucocutaneous pyoderma (MCP) have overlapping

clinical and histopathological changes, often making diagnosis difficult. Histopathological features of 27 nasal

planum biopsies were scored to determine whether DLE and MCP were histopathologically distinguishable.

Long-term follow-up, enabling assessment of clinical diagnoses, was available on 15 cases; 11/15 cases were immuno-

modulatory responsive (ImR) and 4/15 were antibiotic responsive (AbR). Clinical diagnosis, determined by

response to treatment for 15/27 cases, was not predictable based on scoring of histopathological features. Distinct

histopathological patterns were observed: 2/11 ImR cases had a lymphocyte-rich interface dermatitis. All other

cases had the same histopathological changes: a band-like diffuse superficial plasmacytic to lymphoplasmacytic

dermatitis± focal basal cell damage, but different clinical diagnoses (4/4 AbR, 9/11 ImR). German shepherd dogs/

crosses were over-represented (44.4% of the cases) and tended to have more multifocal lesions (41.7% vs. 26.7%

of all other breeds). Longer duration of disease was associated with a preponderance of plasmacytic infiltrate

(P = 0.026).

Keywords: canine, discoid lupus erythematosus, interface, lichenoid, mucocutaneous pyoderma.

INTRODUCTION

The differential list for nasal dermatoses is extensive

and includes canine discoid lupus erythematosus (DLE)

and mucocutaneous pyoderma (MCP).1,2 Discrimina-

tion between these two diseases on the basis of histo-

pathology can be challenging, and dermatopathologists

often report only a morphological diagnosis when

observed changes are not overtly characteristic foreither disease.

Canine DLE has been reported in the literature for

more than 20 years,3,4 and is a benign autoimmune

cutaneous disease initially presenting with depigmenta-

tion, erythema, scaling, and a loss of the normal

cobblestone-like architecture of the nasal planum. With

chronicity, lesions may spread up the bridge of the nose,

becoming more extensive to include erosion, ulceration

and crusting. Lesions may be observed, though less

frequently, on periocular regions, pinnae or genitals.1

The infiltrate present in canine DLE is reported to be

predominantly a lymphocyte-rich interface dermatitis

along the dermoepidermal junction, hair follicles and

adnexal glands. However, it is also reported that this

infiltrate can vary from being primarily lymphocytic

to lymphoplasmacytic and in some cases primarily

plasmacytic. This infiltrate may partially obscure the

dermoepidermal junction and may occur around

superficial and deep vessels. Vacuolar degeneration

may be observed, as well as apoptosis of individualkeratinocytes in the basal cell layer (Civatte bodies),

often with marked pigmentary incontinence, lym-

phocytic exocytosis, and focal basement membrane

thickening.2,5,6 The epidermis is usually hyperplastic

but may have focal areas of atrophy.6 Dermal and epi-

dermal mucinosis may be present.6

There is debate whether DLE, a term borrowed from

human medicine, is properly applied when describing

the canine disease.2,7,8 Therefore, in this paper, the term

lupus-like disease of the nasal planum (LLDN) will be

used to describe cases of nasal dermatitis previously

referred to as ‘canine DLE’, having the following

histopathological features: lymphocyte-rich interfacedermatitis with vacuolar degeneration, apoptosis of

basal cells, and varying degrees of epidermal atrophy

and hyperplasia.

Correspondence: E. A. Mauldin, University of Pennsylvania, School

of Veterinary Medicine, 3900 Delancey St., Philadelphia, PA 19104,

USA. E-mail: [email protected]



342 SP Wiemelt et al.

© 2004 European Society of Veterinary Dermatology, Veterinary Dermatology, 15, 341–348

In dogs, MCP has been reported as a visibly distinct

process from LLDN, presenting with erythema, swelling

and crusting. With chronicity, depigmentation, fissur-

ing, and erosions (primarily involving the lips and

perioral skin) may develop.2,9 Clinically, MCP resolves

with relatively short courses of antibiotics, although

long-term management may be needed as lesions mayrecur.9 In contrast, LLDN does not respond as readily

to short courses of therapy, but is controllable with

long courses of immunomodulatory treatments. MCP

can affect the nares and nasal planum exclusively, and

in this respect is clinically similar to LLDN.9 In MCP,

the infiltrate is described as a dense band-like super-

ficial dermal infiltrate (‘lichenoid’ in some texts),6 which

is predominantly plasmacytic (vs. lymphocytic in

LLDN), and hugs rather than obscures the dermoepi-

dermal junction.2,5,6 Vacuolar degeneration and apop-

tosis of basal cells, evidence of basal cell damage that

is seen in cases of LLDN, are features not seen in MCP.

Despite these reported differences there are many cases

that display overlapping clinical and histopathological

features of LLDN and MCP, making histopatholog-

ical differentiation difficult.

Adding to the difficulty in defining the histopatho-

logical features and the degree to which they must be

present in order to be diagnostic of one of these two

diseases, the terms interface and lichenoid are used

imprecisely and inconsistently in the literature when

describing the inflammatory infiltrate in the superficial

dermis in LLDN and MCP.5,10 Improper use of these

terms will imply that certain histopathological changes

thought to be specific for one of the two diseases arepresent, when they are not. In this paper, the term

interface dermatitis will be used when the dermoepider-

mal junction is obscured by vacuolar degeneration, by

lichenoid (band-like) cellular infiltrate, or by both. A

pattern of inflammation in the superficial dermis that

does not obscure the basement membrane will be

described as a band-like superficial dermatitis, with

additional qualifiers.

This study was designed to determine whether

LLDN and MCP could be distinguished on the basis

of semiquantitative analyses of histopathological

features.

MATERIALS AND METHODS

Case selection criteriaA computer search was performed for canine nasal

biopsy submissions coded as ‘lupus, discoid lupus,

nasal pyoderma, mucocutaneous pyoderma, nasal,

nasal planum, lichenoid and interface’ from in-house

cases submitted to the Diagnostic Service of the

Laboratory of Pathology and Toxicology, University

of Pennsylvania, School of Veterinary Medicine, and

from submissions to the aforementioned laboratory bytwo board-certified veterinary dermatologists during

the time period 01/1994–09/2002. Cases were limited

to those obtained from the nasal planum; any samples

containing only haired skin or samples from other

mucocutaneous junctions were excluded. All cases of

Vogt–Koyanagi–Harada-like syndrome (VKH), pem-

phigus foliaceus and erythematosus, systemic lupus

erythematosus, nasal hyperkeratosis and allergic/contact

dermatitis were excluded.

Clinical featuresThe medical records were reviewed for all cases. The

following information was recorded: signalment,

lesion distribution, duration of lesions prior to biopsy,

any treatments received at the time of biopsy, response

to treatment (antibiotics, topical or systemic steroids,

tetracycline/niacinamide, and others), all diagnostics

performed and abnormal values, description and

progression of lesions previous to biopsy and after

instituting treatment (including date of last clinical

examination and duration of therapy), and original

diagnosis given by the dermatopathologist.

Determination of clinical response to treatmentCases were determined to be either immunomodulat-

ory responsive (ImR) or antibiotic responsive (AbR)

based on reported response to treatment. Response to

immunosuppressive or immunomodulatory treatment

(consistent with an autoimmune process like LLDN)

was assigned to cases in three different categories: (1)

dogs that were treated with antibiotics for more than

21 days at an appropriate dosage, demonstrated mild

to moderate improvement, and proceeded to demon-

strate nearly complete to complete improvement when

placed on immunomodulatory therapy (topical, inject-able or oral steroids, a combination of tetracycline and

niacinamide often with vitamin E or fatty acids, topical

tacrolimus, and in one case azathioprine); (2) dogs that

received antibiotics in combination with any immuno-

modulatory or immunosuppressive treatments and

whose improvement continued beyond the discontinu-

ation of antibiotics to the level of complete resolution

while on immunomodulatory/immunosuppressive

therapy; (3) dogs that had resolution of lesions on

immunomodulatory or immunosuppressive therapy

without concurrent antibiotics. For all cases receiving

tetracycline, the dosage was suboptimal for bacterio-static effect.

Response to antibiotic treatment (consistent with an

infectious process like MCP, which demonstrates

complete cure with a short course of appropriate anti-

biotics) was assigned to dogs in two different categories:

(1) dogs that demonstrated nearly complete to com-

plete resolution on oral antibiotics ± topical antibiotics;

(2) dogs that demonstrated only mild improvement

on oral steroids, and then demonstrated complete resolu-

tion when given oral antibiotics.

Dogs without follow-up (10/27) or those that were

treated appropriately with antibiotics and/or immu-

nomodulatory drugs and had mild or no improvement(2/27) were assigned to the category ‘no response to

therapy’. Thus, response to therapy was evaluated for

a total of 15/27 cases.




Comparing Canine DLE and MCP 343

Histopathological evaluationHematoxylin and eosin-stained slides and Periodic

acid-Schiff stained slides from all cases were reviewed

by two of the authors together (SPW, EAM) and were

reviewed independently by a third author (MHG).

Review of each of the slides was performed in a blinded

fashion, without knowledge of history, prior dia-gnoses, therapeutic treatment or clinical outcome.

A prespecified panel of features were examined and given

a numeric score. The histopathological features used to eval-

uate each section were based on those previously proposed

to distinguish LLDN from MCP and are listed below.2,5,6

Features and scoring

Cells present in the infiltrate: 0 = predominantly

plasmacytic; 1.5 = a mixed inflammatory infiltrate

of lymphocytes, plasma cells, and occasional macro-

phages; 3 = predominantly lymphocytic.

Presence of a deep infiltrate around adnexal glands

and vessels: yes/no.

Degree to which the dermoepidermal junction is

obscured : 0 = not obscured; 1 = obscured focally; 2

= obscured multifocally; 3 = obscured diffusely.

Degree of vacuolar basal cell alteration/degeneration:

0 = no vacuolar degeneration; 1 = focal vacuolar

degeneration; 2 = multifocal vacuolar degeneration;

3 = diffuse vacuolar degeneration.

Number of apoptotic basal cells (Civatte bodies) per high

power field : 0 = no Civatte bodies; 1 = 1 per 10 hpf;

1.5 = 1 per 8 hpf; 2 = 1 per 5 hpf; 2.5 = 1 per 2 hpf;

3 = 1 or > per hpf.

Thickening of basement membrane (the basal lamina

zone): 0 = no thickening; 1 = focal thickening;

2 = multifocal thickening; 3 = diffuse thickening.

Degree of pigmentary incontinence: 0 = no inconti-

nence; 1 = mild, only seen focally at high magnifica-

tion; 2 = moderate, seen focally at low magnification;3 = severe, seen diffusely at low magnification.

Presence of epidermal atrophy: yes/no.

Degree of epidermal hyperplasia: 0 = no hyperplasia;

1 = mild, focal hyperplasia; 2 = moderate, multifocal

hyperplasia; 3 = severe, diffuse hyperplasia.

Lymphocytic exocytosis into the epidermis: yes/no.

Statistical analysesNumeric semiquantitative scores for the features described

above were evaluated statistically using the nonparametricMann–Whitney test for random, independent samples

with nominal values. Those features assigned ordinal (i.e.

yes/no) values were evaluated using the chi-square test.

RESULTS

Clinical data

Signalment. Twenty-seven dogs met the selection cri-

teria. There were 15 female dogs (13 spayed), and 12

male dogs (eight castrated). There were 12/27 Germanshepherd dogs (44%; 10 pure-bred and two crosses),

6/27 mix breeds, a springer spaniel, a cocker spaniel, a

field spaniel, a Samoyed, a collie, a Labrador retriever,

a standard poodle, a greyhound, and an Irish wolf-

hound. Age at presentation ranged from 8 months to

13 years (mean: 7.5, SD: ± 0.6 years). The duration of

nasal dermatitis prior to biopsy ranged from 2 to

48 months (mean: 16.9, SD ± 2.8 months).

Lesion distribution. While all cases had nasal lesions,

9/27 dogs had additional lesions at other locations,

including the lip (6), periocular area (2), vulva (1), scro-

tum (1), and the haired skin of the muzzle (2). Multi-

focal lesions were present on 5/12 (41.7%) German

shepherd/shepherd-crosses, and present on 4/15

(26.7%) of all other breeds, although these differences

were not shown to be statistically significant.

Analysed retrospectively, knowledge of the breed of

the animal and presence of multiple lesions did not

appear to significantly influence the originally assigned

histopathological diagnosis.

Lesion description. Of the 27 cases, 24 were reported to

have crusts, 22 with depigmentation, 16 with erythema,

12 with loss of ‘cobble-stone’ architecture, 11 withulceration, seven with erosions, four with pruritus, four

with a recorded history of waxing and waning, three

with fissures, and two with scale. These reported

lesions did not correspond to any other clinical feature.

Follow-up. Follow-up of greater than 8 weeks (median:

12.0 months, range: 2–36 months) was established in

17 cases. There were 14/17 cases that were re-examined

at least once by the original dermatologist, 1/17 that

was re-examined by the local veterinarian, and 2/17

that had a phone-call follow-up.

Eleven of 17 cases were categorized as immuno-modulatory responsive (ImR). Four of 11 dogs

received an adequate dose and course of antibiotics,

but demonstrated resolution of lesions only after

immunomodulatory drugs were started. Five of 11

dogs received a combination of oral antibiotics and

immunomodulatory drugs. These five dogs continued

to demonstrate improvement after cessation of anti-

biotics. One case never received antibiotics (case

#11), and one case (case #10) recovered after receiv-

ing 6 days of ampicillin followed by extended treat-

ment with tetracycline and niacinamide plus topical

betamethasone.

Of these 11 cases, seven were maintained on animmunomodulatory protocol including tetracycline or

doxycycline. Only 4/11 cases did not receive tetracy-

cline as part of an immunomodulatory treatment





protocol; one case never received any antibiotics

(case #11) and responded completely to oral pred-

nisone; and one case (case #8) was treated with

cephalexin for 6 weeks with moderate improvement,

and subsequently demonstrated complete improve-

ment after discontinuing the cephalexin and starting

topical steroid treatment only. These two cases had a12- and 9-month follow-up, respectively. Another case

(#7) was treated with enrofloxacin and then amoxicil-

lin trihydrate/clavulanate potassium with no improve-

ment. Resolution was then achieved on 0.1%

tacrolimus. The last case (#9) had a moderate response

to sulfadimethoxine/ormetoprim, and then a complete

response to oral steroids. Due to the retrospective

nature of the study the terms ‘complete response’ or

‘resolution’, as given in the record, could indicate that

the appearance of the nasal planum had returned

to normal, or that a dramatic improvement in lesions

was observed and additional improvement was not

expected. All 11 cases were either maintained on

immunomodulatory therapy or, in cases where it was

discontinued, lesions became worse and immuno-

modulatory treatment had to be re-instituted, indicating

that in these cases the disease process was controllable

but not curable.

Four of 17 cases were antibiotic responsive (AbR).

The duration of antibiotic treatment ranged from

4 weeks (case #12) to greater than 10 weeks (case #15).

One dog improved mildly while receiving oral steroids,

resolving completely when treated with oral anti-

biotics. Case #12 was the only one of four that was

also treated with a topical antibiotic (mupirocin), andthe only case where follow-up indicates recurrence of

lesions after cessation of topical antibiotic treatment.

Case #15 had recurrent bronchopneumonia that was

treated intermittently with oral and injectable antibiot-

ics for more than 1.5 years.

Therapeutic responsiveness could not be classified

for 2/17 dogs with follow-up. Case #16 was treated

with oral and topical antibiotics for greater than

1 month with only mild to moderate improvement;

immunomodulatory drugs were not administered.

Case #17 was treated with culture-based oral antibiotics

for 30 days with modest improvement, topical andoral steroids for greater than 1 month with no improve-

ment, and a combination of tetracycline and niacina-

mide for 3 months with no improvement.

Histopathological evaluationAll reviewers noted that there were cases with a

lymphocyte-rich interface dermatitis, with apoptosis and

vacuolar degeneration of the basal cells (LLDN) that

were easily distinguishable from other cases. Therefore,

each slide was subsequently assigned one of three pat-

terns. These patterns were not equivalent to a clinical

diagnosis or response to therapy:

1 Pattern L (LLDN): Presence of a lymphocyte-rich

interface dermatitis with apoptosis and vacuolar

degeneration of the basal cells (Fig. 1).

2 Pattern M (MCP-like): Presence of a band-like

diffuse superficial plasmacytic dermatitis with

minimal evidence of basal cell damage (Fig. 2).

3 Pattern M/L: A dermatitis demonstrating varying

degrees of features present in patterns L and pattern

M. The superficial dermal infiltrate was lympho-

plasmacytic, with focal evidence of basal cell damage.

A histopathological pattern was assigned to all cases

(17/27) that were available for follow-up (Table 1). All

authors reported only two cases with a lymphocyte-

rich interface dermatitis with apoptosis and vacuolar

degeneration of the basal cells (pattern L; Fig. 1).

However, authors’ opinions varied when assigning pat-

terns to some cases not definitively pattern L (Table 1;

Fig. 3). The 10/17 cases that were not available for

follow-up were then reviewed by all authors (data

not shown), and none of these cases were classified as

pattern L by any of the reviewers.

Numeric scores for predefined histopathological fea-

tures were recorded for all 27 cases (data not shown).

Comparing histopathological and clinical data

Pattern assessment vs. response to treatment. When

comparing response to treatment to the patterns

assigned, the two cases with pattern L (Table 1, cases

#10 and #11) responded to immunomodulatory treat-

ment. Neither of these cases had received antibiotics or

was on any treatment at the time of biopsy. One of

these cases (#11) had never received antibiotics and

demonstrated complete improvement on a long course

of oral prednisone, while the other case (#10) received

only 6 days of ampicillin, and demonstrated complete

response when placed on a combination of tetracycline

and niacinamide plus topical betamethasone. These

cases had a follow-up of 12 and 24 months, respectively.Of the 15 cases that were not definitively pattern L,

five cases were classified as pattern M in both reviews.

Of these five cases, three were immunomodulatory

Figure 1. Pattern L, case #10. Diffuse predominantly lymphocytic

infiltrate in the superficial dermis, obscuring the dermoepidermal

unction (H&E, ×10, bar = 50 µm).





responsive, and two were antibiotic responsive. One of

the fifteen cases was classified as pattern M/L in both

reviews, and was antibiotic responsive. The remaining9/15 cases were classified as pattern M by one reviewer,

and M/L by the other. Six of these nine cases were

immunomodulatory responsive, 1/9 was antibiotic

responsive, and therapeutic responsiveness (clinical

diagnosis) could not be assigned to 2/9 cases (#16 and

17) (Table 1).

Histopathological features vs. response to treatment.

There were no significant differences when scores for

each of the histopathological features were compared

between cases that were immunomodulatory respons-

ive or antibiotic responsive (Table 2). Therefore, noneof these individual features could predict the response

to therapy, and therefore could not help to distinguish

an autoimmune from an infectious process.

Duration of clinical signs and character of cellular

infiltrate. The mean duration (months) of clinical signs

before biopsy for all cases (6/27) with a ‘character of

cellular infiltrate’ score of 0 was found to be signi-

ficantly longer (mean: 28.5 ± 16.1 months) than the

mean duration for all cases (21/27) with an infiltrate

score of 1.5 or higher (mean: 13.5 ± 12.5 months;

P = 0.026). The two cases that responded to immuno-

modulatory treatment and which received a patternL were both assigned an infiltrate score of 3 (e.g. pre-

dominantly lymphocytic infiltrate), and had durations

of 12 and 36 months.

Table 1. Characterization of cases by response to therapy or

pattern type

Case #

Response

to therapy*

Review

(EAM, SPW)†

Review

(MHG)†

1 ImR M M/L

2 ImR M M

3 ImR M M/L4 ImR M M/L

5 ImR M M

6 ImR M M

7 ImR M M/L

8 ImR M/L M

9 ImR M/L M

10 ImR L L

11 ImR L L

12 AbR M M

13 AbR M M

14 AbR M M/L

15 AbR M/L M/L

16 – M M/L

17 – M/L M

*Cases were designated as immunomodulatory responsive (ImR) orantibiotic responsive (AbR).

†Pattern types were assigned ‘L’ (presence of a lymphocyte-rich

interface dermatitis with apoptosis and vacuolar degeneration of the

basal cells); ‘M’ (presence of a band-like diffuse superficial

plasmacytic dermatitis with minimal evidence of basal cell damage);

or ‘M/L’ (dermatitis demonstrating varying degrees of features

present in pattern M and pattern L. The superficial dermal infiltrate

was lymphoplasmacytic, with focal evidence of basal cell damage).

Figure 2. (a) Pattern M, case #13. Epidermal hyperplasia with a

diffuse plasmacytic superficial dermal infiltrate and marked

pigmentary incontinence, with mild vacuolar degeneration and

occasional apoptotic basal cells (H&E, ×10, bar = 50 µm). (b) Pattern

M, case #13. Higher magnification. Mild vacuolar degeneration

with central apoptotic keratinocyte (H&E, ×20, bar = 20 µm).

Figure 3. Depending on reviewer pattern M or M/L, case #3.

Epidermal hyperplasia with diffuse plasmacytic superficial dermalinfiltrate and mild multifocal vacuolar degeneration and occasional

apoptotic basal cells (H&E, ×10, bar = 50 µm).





Original histopathological diagnosis assigned andresponse to treatmentThere was no correlation between the original his-

topathological diagnosis assigned to cases and the

clinical response to treatment.

DISCUSSION

For more than 20 years, the term ‘canine DLE’ has

been used to refer to a disease that presented with

varying degrees of erythema, crusting, erosions,

ulcerations, hypopigmentation, and loss of the ‘cobble-

stone’ architecture of the nasal planum. The lesions

may wax and wane and are often photosensitive.

Although the exact pathomechanism of the disease has

not been elucidated, it is thought to be an autoimmune

process.

There is the sense among some veterinary patholo-gists and dermatologists that some cases of nasal der-

matitis that behave clinically as ‘canine DLE’/LLDN

(e.g. controlled with immunomodulatory treatment)

cannot be readily distinguished by histopathology

from MCP. Indeed, in this study three cases that were

immunomodulatory responsive (cases #2,5,6) could

not be distinguished from two antibiotic-responsive

cases (#12 and 13) on the basis of histopathology

(e.g. all cases were assigned the same pattern (M) by re-

viewers). There were other cases that were all immuno-

modulatory responsive, but had different histopathological

patterns (e.g. patterns M, M/L, and L). Several hypo-theses have been proposed to explain why these cases

with the same response to therapy could demonstrate

different patterns (pattern L vs. patterns M and M/L):

(1) There may be more than one histopathological and

clinical pattern consistent with an autoimmune disease

of the nasal planum;11 (2) histopathological changes in

canine nasal dermatitis may occur along a continuum;

(3) plasma cells, resulting from secondary infection,

may complicate identification of lymphocytes (thus

shifting a pattern L to a pattern M or M/L); (4) mucous

membranes and mucocutaneous tissue will respond to

any form of injury that elicits a chronic inflammatory

cell response with a plasmacellular subepidermalinfiltrate.6 Therefore, any trauma (rubbing, licking,

scratching, etc.) to the nasal planum of a dog with LLDN

may result in a plasmacellular infiltrate admixed with

lymphocytes; recognition of the lymphocyte-rich pattern

in these cases would be difficult.

In this study, neither pattern assessment nor semi-

quantitative evaluation of key histopathological features

was successful in predicting response to treatment for

a majority of the cases. However, pattern recognition

was useful in distinguishing cases with plasmacytic

lymphoplasmacytic, band-like superficial dermatitis

(pattern M and M/L, respectively) from those cases

with a predominantly lymphocyte-rich interface der-

matitis (pattern L). When evaluating the histopathology

of each case blindly, all reviewing authors identified the

same two cases as having a lymphocyte-rich interface

dermatitis (pattern L). Although these two cases

responded to immunomodulatory therapy, more cases

are needed to confirm that all cases of pattern L would

be immunomodulatory responsive. The reviewing

authors’ assignment of pattern varied in some cases

that were not clearly pattern L, confirming that themost confusing cases for the dermatopathologist to

diagnose are those cases with a plasmacytic to lympho-

plasmacytic infiltrate and evidence of mild basal cell

damage. With the current understanding of histo-

pathology associated with these diseases, unless a case

has features that are clearly pattern L, a consistent pat-

tern and diagnosis cannot be assigned. Because cases

that were not classified as pattern L did not respond

uniformly to treatment (e.g. some were antibiotic res-

ponsive while others were immunomodulatory respons-

ive, and some did not respond to therapy), it is likely

that these cases (patterns M and M/L) representedboth infectious and autoimmune diseases.

The fact that a predominantly plasmacytic infiltrate

was significantly associated with duration is consistent

with known immunological mechanisms. This finding

must be considered when evaluating the character of a

particular infiltrate. Although a predominantly plas-

macytic infiltrate is suggestive of MCP, it could be

hypothesized that older, infected cases of LLDN would

appear similar. However, given that the two pattern L

cases in this study had a duration of 12 months and

36 months, and neither were treated with antibiotics

prior to biopsy, it is evident that not all chronic pattern

L cases will eventually become infected.German shepherd dogs and their crosses were over-

represented in cases of nasal dermatitis and tended

to have more multifocal lesions than other breeds.

Histopathological feature measured

P-values* when comparing means from

ImR cases (n = 11) to AbR cases (n = 4)

Character of infiltrate at dermoepidermal junction 0.332

Vacuolar degeneration 0.199

Apoptotic basal cells 0.136

Pigmentary incontinence 0.325

Lymphocytic excocytosis Not significant (chi-square)

Basement membrane thickening 0.50

Epidermal hyperplasia 0.73

Atrophy Not significant (chi-square)

*P-values derived from Mann–Whitney statistical test, except where otherwise noted.

Table 2. Statistical evaluation of mean

scores when histopathological features were

quantified from cases that were

immunomodulatory responsive (ImR) or

antibiotic responsive (AbR)





Interestingly, none of the German shepherd dogs or

crosses had a pattern L infiltrate.

There are several caveats to note with this study.

Because of the retrospective nature of the study, the

approach to therapy and measurement of improve-

ment on therapy was not standardized. Therefore,

when the terms ‘complete resolution’ or ‘completeresponse’ were reported, it is not clear if the nasal pla-

num appeared physically normal to the clinician, or if

the terms were used to indicate a dramatic improve-

ment of lesions and additional improvement was not

expected. In either case these terms were used to

describe the lesions and not whether the disease pro-

cess was cured or simply controlled by treatment. This

is especially important to note in cases that were cat-

egorized as ImR. A disease process that is responsive

to immunomodulatory therapy, and therefore likely

autoimmune, may be controlled, but not cured, with

long-term treatment. The amount of information

available from the records regarding follow-up varied

tremendously and may have affected evaluation of

each case’s response to treatment. A more complete

and specific clinical description with regard to sym-

metry, atrophy, degree of crust formation vs. presence of

scale and exact location on the nasal planum may have

added clinical information that could have been cor-

related to the histopathological patterns. The small

number of cases available for this study, particularly

those with sufficient follow-up to allow an assessment

of response to treatment, was also a limitation. Any

attempt to standardize histopathological evaluation is

limited by the reviewer’s skill and subjective nature of the measurement. This is compounded by the fact that

histopathological sections of nasal planum are not

uniformly affected in these disease processes.

The findings of this study show that in many cases of

nasal dermatitis, histopathological changes can not

predict response to treatment, and thereby distinguish

an autoimmune from an infectious process.

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Résumé Le lupus discoïde canin (DLE) et la pyodermite cutanéomuqueuse (MCP) ont des aspects cliniques et

histopathologiques communs, rendant le diagnostic difficile. Dans cette étude, 27 biopsies de la truffe ont été

étudiées pour déterminer si le DLE et la MCP étaient différenciables sur le plan histopathologique. Un suivi aulong cours, permettant un diagnostic clinique, était disponible dans 15 cas. 11/15 ont bien répondu à l’immuno-

modulation (ImR) et 4/15 aux antibiotiques (AbR). Le diagnostic clinique, déterminé par la réponse thérapeu-

tique pour 15/27 cas, n’a pas pu être prédit par l’aspect histopathologique. Des patrons histopathologiques dif-

férents ont été observés: 2/11 cas d’ImR avaient une dermatite d’interface riche en lymphocytes. Tous les autres

cas avaient un aspect histopathologique semblable: dermatite diffuse, en bande superficielle, plasmocytaire ou

lymphoplasmocytaire,± atteinte des cellules de la basale, mais des diagnostics cliniques différents (4/4 AbR, 9/

11 ImR). Les Berger allemand ou leurs croisés étaient sur-représentés (44.4% des cas) et avaient tendance à

présenter des lésions plus multifocales (41.7% versus 26.7% pour les autres races). Une durée plus longue d’évo-

lution était associée à une prédominance de plasmocytes dans l’infiltrat (P = 0.026).

Resumen El lupus discoide canino (DLE) y la pioderma mucocutánea (MCP) presentan cambios clínicos e histo-

patológicos comunes, dificultando a menudo el diagnóstico. Se estudiaron las características histopatológicas

de 27 biopsias de plano nasal para determinar si el DLE y la MCP eran distinguibles histopatológicamente. Se

pudo realizar un seguimiento a largo plazo, permitiendo valorar los diagnósticos clínicos en 15 casos; 11/15 casos

respondieron a terapia inmunomoduladora (ImR) y 4/15 respondieron a antibióticos (AbR). El diagnóstico

clínico, determinado por la terapia al tratamiento en 15/27 casos, no podía predecirse basándonos en la puntuación

de las características histopatológicas. Se observaron características histopatológicas definibles: 2/11 casos de





ImR tenían una dermatitis de la unión rica en linfocitos. Los demás casos mostraron las mismas alteraciones

histopatológicas, una dermatitis superficial en banda difusa plasmacítica a linfocítica ± daño focal de células

basales, pero con diferentes diagnósticos clínicos (4/4 AbR, 9/11 ImR). Los perros Pastor Alemán y sus cruces

se encontraban sobre-representados (44.4% de los casos) y tendían a tener más lesiones multifocales (41.7% ante

26.7% de todas las razas). Se asoció una mayor duración de la enfermedad con un predominio de infiltrado

linfocítico (P = 0.026).

Zusammenfassung Caniner diskoider Lupus erythematodes (DLE) und mukokutane Pyodermie (MCP) haben

sich überschneidende klinische und histopathologische Veränderungen, was die Diagnose oft schwierig macht.

Histopathologische Merkmale von 27 Biopsien vom Planum nasale wurden ausgewertet, um zu bestimmen, ob

DLE und MCP histopathologisch unterscheidbar sind. In 15 Fällen war ein Langzeit-Follow-up, das die

Bewertung der klinischen Diagnose ermöglichte, verfügbar; 11/15 Fälle reagierten auf immunmodulatorische

Therapie (ImR) und 4/15 auf Antibiotika-Therapie (AbR). Die klinische Diagnose, gestellt durch Therapieerfolg

bei 15/27 Fällen, war basierend auf Auswertung histopathologischer Veränderungen nicht voraussagbar. Unter-

schiedliche histopathologische Muster wurden beobachtet: 2/11 ImR Fälle zeigten eine Interface-Dermatitis, die

reich an Lymphozyten war. Alle anderen Fälle zeigten dieselben histopathologischen Veränderungen: eine

bandförmige diffuse superfizielle plasmazytäre bis lymphoplasmazytäre Dermatitis ± fokale Schädigung der

Basalzellen, aber unterschiedliche klinische Diagnosen (4/4 AbR, 9/11 ImR). Deutsche Schäferhunde und

Schäferhund-Mischlinge waren überpräsentiert (44,4% der Fälle) und tendierten zu mehr multifokalen Läsionen

(41,7% gegenüber 26,7% bei anderen Rassen). Längere Erkrankungsdauer war mit einem Vorherrschen eines

plasmazytären Infiltrates verbunden (P = 0.026).

A Retrospective Study Comparing the Histopathological Features and Response to Treatment in Two...

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