Vet Dermatol 2016 DOI: 10.1111/vde.

12389

Clinical and microscopic features of generalized discoid

lupus erythematosus in dogs (10 cases)
Frane Banovic*†‡, Keith E. Linder‡§, Maarja Uri†¶, Michael A. Rossi** and Thierry Olivry†‡
*Department of Small Animal Medicine and Surgery, College of Veterinary Medicine, University of Georgia, 2200 College Station Road, Athens,
GA 30602, USA
†Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, 1060 William Moore Drive, Raleigh, NC 27607,
USA
‡Comparative Medicine Institute, North Carolina State University, Raleigh, NC 27607, USA
§Department of Population Health and Pathobiology, College of Veterinary Medicine, North Carolina State University, 1060 William Moore Drive,
Raleigh, NC 27607, USA
¶Small Animal Clinic, Estonian University of Life Sciences, Kreutzwaldi 1, Tartu 51014, Estonia
**Veterinary Skin and Allergy Specialists, Veterinary Referral Center of Colorado, 3550 South Jason Street, Englewood, CO 80110, USA
Correspondence: Thierry Olivry, NC State University, College of Veterinary Medicine, 1060 William Moore Drive, Raleigh, NC 27607, USA. E-mail:
tolivry@ncsu.edu

Background – Generalized discoid lupus erythematosus (GDLE) is a newly recognized canine variant of chronic
cutaneous lupus erythematosus (CLE) that is not well characterized.
Hypothesis/Objectives – We report herein the signalment, clinical signs, treatment outcome, histopathology
and immunological findings of 10 dogs with GDLE.
Methods – Inclusion criteria were: (i) a >3 month history of generalized skin lesions indicating a chronic or recur-
rent nature; (ii) skin lesions resembling those of human GDLE; (iii) histopathology of CLE (lymphocyte-rich inter-
face dermatitis). Direct immunofluorescence (IF) and antinuclear antibody serology were investigated whenever
possible.
Results – Various breeds were affected in their mid- to late adulthood. Selection criteria of generalized multifo-
cal, annular (“discoid”) to polycyclic plaques with pigment changes, erythematous margin, adherent scaling,
follicular plugging and central alopecia were shown in all dogs. In nine dogs, plaques contained mild to moderate
central scarring with depigmentation and/or hyperpigmentation. There were no dogs in which the disease pro-
gressed to systemic lupus erythematosus within a median follow-up of 2.5 years. Per inclusion criteria, interface
dermatitis occurred with basement membrane zone (BMZ) thickening, suprabasal apoptosis and/or dermal fibro-
sis in some dogs. Infundibular interface folliculitis was common; it sometimes transitioned to mural folliculitis in
lower follicle segments, and occurred with follicular and sebaceous gland atrophy. The direct IF revealed patchy
deposition of immunoglobulin IgG and IgM at the BMZ. Lesions responded to a variety of treatments, including
ciclosporin, hydroxychloroquine, topical tacrolimus and tetracycline/niacinamide. Relapses were common after
medications were tapered.
Conclusions and clinical importance – These observations support the existence of a canine homologue of
human GDLE.

of individual skin lesions.1 A purely histological classifica-

Introduction
In humans, the Sontheimer–Gilliam classification divides
the skin lesions that can be encountered in lupus erythe-
matosus (LE) into those with characteristic microscopic
changes of lymphocyte-rich interface dermatitis with
basal keratinocyte damage (i.e. “lupus-specific” skin dis-
eases = cutaneous LE or CLE) and those without such
microscopic pattern (i.e. “LE-nonspecific” skin dis-
eases).1,2 Furthermore, LE-specific skin diseases are sub-
divided into acute, subacute and chronic types (i.e. ACLE,
SCLE and CCLE, respectively);1 these designations refer
to both the lesional morphology and the average duration
Accepted 24 August 2016
Sources of Funding: This study was self-funded.
Conflict of Interest: No conflicts of interest have been declared.
tion is impossible, because a significant overlap exists
between the various clinical subtypes of CLE.3
Among the several variants of human CCLE [e.g. dis-
coid LE (DLE), verrucous (hyperkeratotic) LE, chilblain LE,
lupus tumidus and lupus profundus], DLE represents the
most common form: it is divided into a localized variant
where skin lesions are confined to the head and neck,
and the generalized form, in which skin lesions also occur
below the neck.4 The classic skin lesions of human DLE
usually consist of early erythematous and variably scaly
macules or papules that slowly evolve into coin-shaped
(i.e. discoid) plaques with adherent scales, follicular plug-
ging (i.e. comedones) and peripheral hyperpigmentation
presumed to occur secondarily to inflammation. These
discoid plaques can coalesce and develop central scarring
and depigmentation.4 Atypical presentations of general-
ized DLE have been reported in patients of differing

© 2016 ESVD and ACVD, Veterinary Dermatology 1

Banovic et al.
ethnic groups, such as Indian people from the Asian sub-
continent.5–8 In these patients, the morphological appear-
ance of lesions can vary from hyperpigmented macules5,6
to hyperkeratotic, hyperpigmented plaques with erythe-
matous border.7,8
At this time, well characterized manifestations of
canine CLE that fall under the category of CCLE include
the long recognized, localized, facial-predominant DLE,9–11
exfoliative CLE (ECLE) of German shorthaired pointers12
and mucocutaneous lupus erythematosus (MCLE).13
Several single case reports have suggested the
existence of other generalized variants of CCLE in
dogs.14–17
The purpose of this paper is to describe the clinical fea-
tures, histopathology, immunopathology and treatment
outcome of 10 dogs with skin lesions resembling those
of generalized DLE (GDLE) of humans. Herein, we pro-
pose canine GDLE to be a second variant to be added to
the classic facial (i.e. localized) DLE first reported in dogs
in 1979.9
Materials and methods
Case selection
Electronic medical records of canine CCLE cases prospectively col-
lected at North Carolina State University’s Veterinary Hospital Derma-
tology Service between 2009 and 2015 were reviewed. One other
case was added after an ad hoc questionnaire was sent to the Vet-
Derm list (vetderm@lists.ncsu.edu). Dogs were included if they ful-
filled all of the following three criteria:
1 a >3 month history of generalized skin lesions indicating their
chronic or recurrent nature;
2 the presence of skin lesions resembling those of human GDLE;
that is the presence of annular (discoid) to polycyclic plaques
with dyspigmentation, adherent scaling, follicular plugging and
central alopecia below the neck);
3 the presence of microscopic lesions typical of CLE (i.e. a lym-
phocyte-rich interface dermatitis with basal cell damage).
Dogs with macular, vesiculobullous, typical and atypical target skin
lesions, and histopathological findings of cytotoxic lymphocytic inter-
face dermatitis with keratinocyte apoptosis occurring throughout
multiple epidermal layers suggestive of erythema multiforme variants
[minor (EMm) and major (EMM)]18 were excluded. We also did not
include German shorthaired pointers with lesions typical of ECLE12 or
dogs with skin lesions characteristic of MCLE.13
Histopathology
Histopathological changes were identified and scored for severity
in haematoxylin and eosin-stained skin biopsy sections. Changes
were scored subjectively as absent, mild, moderate or marked and
the results provided normally reflected the most developed lesional
area identified in a set of biopsies. Because a cell-rich lymphocytic
interface dermatitis was an inclusion criterion, histological sections
were evaluated for morphological variation, distribution and severity
thereof. The severity of keratinocyte apoptosis and lymphocytic
satellitosis of apoptotic cells in the basal layer of the epidermis
were scored separately from that in suprabasal layers. Dispersal of
epidermal pigment to dermal macrophages (pigmentary inconti-
nence), epidermal hyperpigmentation, epidermal ulcers, atrophy,
hyperplasia and hyperkeratosis were also scored, and the presence
of orthokeratosis and parakeratosis was noted. Basement mem-
brane zone (BMZ) thickening, dermal fibrosis and the severity of
lichenoid inflammatory infiltrates (subepidermal band-like infiltrate
of inflammatory cells) were graded and the predominant inflamma-
tory cell types were recorded. Hair follicles were evaluated for
2 © 2016 ESVD and ACVD, Veterinary Dermatology
inflammatory infiltrates at all levels (folliculitis patterns), ker-
atinocyte apoptosis, follicular atrophy, infundibular hyperkeratosis
and perifollicular fibrosis. Sebaceous gland inflammation and atro-
phy were recorded.
Direct immunofluorescence (IF)
In order to detect the presence of immunoglobulin (IgG, IgA, IgM)
and activated complement C3 deposits along the BMZ, direct IF was
performed as described previously.12 The frequency, distribution (in-
cluding extension along the basement membrane of hair follicles)
and characteristics of deposits were described subjectively. The
detection of a thin-to-thick linear deposit at the BMZ, either continu-
ous or interrupted (i.e. patchy), was considered a positive “lupus
band test” (LBT).19
Evaluation for systemic lupus erythematosus
In order to rule out concurrent systemic lupus erythematosus (SLE),
further investigations included combinations of serum antinuclear
antibodies (ANA) titre, serum chemistry profile, complete blood
count and urinalysis. The detection of serum ANA was performed
using a variety of techniques depending upon the laboratory used for
such testing.
Clinical management and prognosis
Data on signalment, history, clinical signs and treatment outcome for
each case were collected and analysed. Details on previous, initial
and maintenance immunosuppressive therapy (dose, frequency and
length of treatment for each drug or combination of drugs) were
reviewed for each case. Additionally, any adverse effects related to
drug therapy, concurrent diseases and frequencies of initial disease
relapses were reported.
Results
Clinical summary
Ten dogs met the inclusion criteria. Three of the cases
included herein have been previously published as single
case reports.14,16,17
Selected dogs included seven pure bred and two cross
bred dogs: two were Chinese crested dogs and Labrador
retrievers; there was one each of the following pure
breeds: miniature pinscher, Leonberger, shih tzu and toy
poodle. The age of onset of GDLE skin lesions varied
between five and 12 years of age (median 9 years),
whereas the female-to-male ratio was one; all dogs were
castrated. Three dogs had a previous history of a skin dis-
ease: one dog each suffered from either cutaneous
melanocytoma, atopic dermatitis or liver associated
necrolytic migratory erythema (NME).
Before the initial visit, skin lesions had been present
between 3 and 24 months (median: 9 months). The initial
lesions most commonly reported by the owners were
erythematous macules, papules and plaques with ero-
sions and scaling; these were first noticed usually on the
neck and trunk. Upon presentation all dogs had lesions on
the neck, dorsum and lateral thorax. Lesions were also
present on the head in seven of 10 cases (70%), whereas
abdomen and medial and lateral aspects of proximal limbs
were affected in eight dogs (80%). According to the inclu-
sion criteria, skin lesions included generalized multifocal,
annular (discoid) to polycyclic plaques with dyspigmenta-
tion, an erythematous margin, adherent scaling, follicular
plugging and central alopecia (Figure 1). In nine dogs
(90%), the plaques evolved with mild to moderate ulcera-
tions, central atrophic or hypertrophic scarring and
 Canine generalized discoid lupus

a b

c d

Figure 1. Typical skin lesions of generalized discoid lupus erythematosus (GDLE) in dogs at initial presentation (a) Two annular hyperpigmented
plaques with focal central depigmentation and scarring (Case 2). (b) An annular to polycyclic plaque consisting of central alopecia, erythema, depig-
mentation and atrophic scarring with peripheral hyperpigmented rim and scaling (Case 3). (c, d) Annular “coin-shaped” plaques with characteristic
depigmentation, atrophic (c) and hypertrophic (d) scarring at inactive centre and hyperpigmentation with erosions and adherent scaling at periph-
eral active border (Case 5).

pigmentation changes (depigmentation and hyperpig-
mentation; Figure 1). Generalized hyperpigmented to
depigmented macules/patches with occasional thick
adherent scaling, central alopecia and erythematous mar-
gin were seen in nine dogs (90%; Figure 2). In one apricot
miniature poodle, reddish brown patches and plaques
with large scales were present throughout the body, and
there was extensive spontaneous alopecia that occurred
even outside of the more focal inflammatory lesions (Fig-
ure 3).
Four dogs (40%) had mucocutaneous regions involved
with plaques appearing most commonly on or around the
genitalia (Figure 4). One Chinese crested dog concur-
rently had depigmentation, deep erosions and loss of
architecture of the nasal planum (Figure 4). Hyperpig-
mented macules/plaques with adherent scaling and follic-
ular plugging were observed on the concave pinnae and
© 2016 ESVD and ACVD, Veterinary Dermatology
caudal (lateral) ear margins of three dogs (Figure 5a,b).
An unusual pattern of reticulated (net-like) hyperpigmen-
tation was visible on the ventral abdomen and lateral tho-
rax in two cases (Figure 5c,d).
There were no systemic signs observed in any dog,
apart from the pruritus and pain at the site of lesions in
four (40%) and three dogs (30%), respectively. A com-
plete blood count revealed mild regenerative anaemia,
serum chemistry results included mild hypoalbuminemia
and moderate elevations of liver enzymes in two of
10 dogs (20%), whereas urinalysis results were unre-
markable in all dogs.
Histopathology
A total of 25 biopsy specimens were evaluated (2–4 per
dog). The cell rich lymphocytic interface dermatitis was
present in all cases (this was an inclusion criterion,
3
Banovic et al.

a b

c d

Figure 2. Close up of the macular/patch type skin lesions present on the thorax of dogs with GDLE (a) Well demarcated annular to polycyclic
hyperpigmented patches with severe adherent scaling, partial alopecia and mild scarring in the centre (Case 10). (b) Well demarcated annular
hyperpigmented macules to patches with prominent follicular plugging, scaling, peripheral erythematous rim and central ulceration (Case 3). (c, d)
Hyperpigmented annular macules and patches with central loss of tissue architecture and prominent silver adherent scales surrounded by a mild
peripheral erythematous margin (d) (Case 7).

however). Moderate to marked basal cell degeneration,
also an inclusion criterion, consisted of keratinocyte vac-
uolation, apoptosis and/or disappearance (Figure 6). The
distribution of these lesions varied from diffuse to focal or
peri-ulcerative; in two cases the severity of basal cell
injury led to microscopic intrabasal cleft formation. Apop-
tosis in suprabasal epidermal layers (Figure 7) was fre-
quently observed (eight of 10; 80%): it was mild (1–10
cells per biopsy section) in five cases (50%) and moder-
ate (10–25 cells per section) in three others (30%). Over-
all, the suprabasal apoptosis was less severe than the
interface change observed for each case. Lymphocytic
satellitosis of apoptotic basal cells (Figure 6) was robust
and present in all cases, whereas the lymphocyte target-
ing of apoptotic suprabasal cells occurred in fewer dogs
(four of eight; 50%). Similarly, lymphocytic exocytosis
was prominent in the deep epidermis and was absent or
mild in superficial epidermal layers. Foci of epidermal atro-
phy were uncommon (three of 10; 30%), and most cases
(seven of 10; 70%) exhibited mild to moderate, diffuse,
epidermal hyperplasia. Interface dermatitis was associ-
ated with foci of partial epidermal collapse, with flattening
and elongation of keratinocytes occurring in an otherwise
hyperplastic epidermis (Figure 6). A mild and occasionally
marked orthokeratotic hyperkeratosis occurred in most
cases with occasional interruption by foci of parakerato-
sis. Moderate to marked pigmentary incontinence colo-
calized with foci of epidermal depigmentation and/or
areas of epidermal hyperpigmentation in all cases.
Moderate to marked BMZ thickening was detected in
focal areas in several cases (six of 10; 60%).
A focal to diffuse and mild to marked lichenoid, dermal
inflammatory infiltrate composed of lymphocytes mixed
with a similar amount or fewer plasma cells was seen in
eight cases (80%; Figure 6). In two dogs that lacked the
lichenoid infiltrate, as well as in cases where lichenoid
infiltrates showed limited distribution in comparison to
the interface dermatitis, the lymphocytes were still
numerous in the basal epidermal layer. A mild perivascu-
lar inflammatory pattern was observed in the superficial

4 © 2016 ESVD and ACVD, Veterinary Dermatology


a b
c d
Figure 3. Skin lesions of generalized discoid lupus erythematosus in an apricot poodle. Generalized brown coloured patches and plaques with
large scales and extensive spontaneous alopecia throughout the body (a, b, d) and involving the dorsum of head and ears (c) (Case 9).
dermis, whereas the middle and deep dermis usually con-
tained minimal or no inflammation (Figure 6). A mild to
marked superficial, laminar dermal fibrosis (five of 10;
50%) extended from the BMZ, and was sometimes pau-
cicellular. Occasional ulcers (four of 10; 40%) were asso-
ciated with mild neutrophilic dermatitis and crusts.
Lesions indicative of vasculitis or panniculitis were not
observed in any section.
Histological changes in adnexa were evaluated for eight
of 10 dogs (80%), excluding the two hairless Chinese
crested dogs. Mild to moderate perifollicular lymphoplas-
macytic inflammation was observed in all eight cases; the
inflammation surrounded the infundibulum and tapered
inwards through the level of the isthmus (Figure 8). A
moderate to marked lymphocytic interface folliculitis
involved the hair follicle infundibula of these eight cases,
and the changes were similar to the basal cell degenera-
tion, suprabasal apoptosis and lymphocytic exocytosis
with satellitosis observed in the epidermis (Figure 8). The
interface folliculitis that extended to the isthmus was usu-
ally mild and occasionally moderate; however, this dis-
tinction was difficult to make in cases of advanced
follicular atrophy. Lymphocytic mural folliculitis (Figure 8)
was mild to moderate in the infundibulum of seven cases
(88%) and usually milder in the lower follicular segments
of all cases. Scattered individual and loose clusters of
lymphocytes infiltrated the external root sheath of anagen
© 2016 ESVD and ACVD, Veterinary Dermatology
Canine generalized discoid lupus
stage, telogen stage and atrophic follicles. Very rarely,
occasional individual lymphocytes infiltrated an anagen
hair bulb. Hair follicle atrophy was observed in all cases
and (Figure 8) ranged from diffuse and advanced to focal
and mild, with atrophic follicles sometimes bordering ana-
gen follicles. Sebaceous gland atrophy was also seen in
all dogs and was more commonly associated with
atrophic hair follicles; the severity ranged from mild and
partial in at least one biopsy. The inflammation within the
glands was limited to the walls of sebaceous ducts that
sometimes contained a few lymphocytes; infiltration of
sebaceous gland lobules was not observed. Follicular
hyperkeratosis and infundibular dilation were mild or
absent in most cases. Perifollicular fibrosis was uncom-
mon (one of eight cases; 13%), mild and restricted to the
infundibulum.
Immunopathology
Antinuclear antibody serology was determined for eight
of 10 dogs (80%) and low ANA serum titres (1:20–1:40)
were detected in seven of these eight cases (88%).
Although ANA serology was positive at low dilutions in
most dogs, the lack of systemic signs and laboratory
results to suggest renal or haematological involvement
excluded a diagnosis of coexisting SLE.20 Direct IF
revealed fine to thick, patchy deposition of IgG and IgM
along the dermo-epidermal junction of lesional paraffin-
5
Banovic et al.

a b

c d

Figure 4. Skin lesions affecting mucocutaneous junctions in dogs with GDLE (a) Well-demarcated bilaterally symmetrical diffuse hyperpigmenta-
tion with adherent scaling and partial alopecia on the muzzle, including periocular areas. Central depigmentation, scarring and ulcerations involve
the nasal planum and bilaterally the medial canthus of the eyes (Case 5). (b) Multifocal hyperpigmented macules with mild erythematous rim on
prepuce (Case 5). (c) Anal/perianal diffuse hyperpigmentation with multifocal depigmentation, scarring and adherent scaling. Note the linear ulcera-
tions in friction areas; this case suffered from liver associated necrolytic migratory erythema. The development of GDLE type skin lesions in this
area is suggestive of the Koebner phenomenon (Case 5). (d) Diffuse hyperpigmented alopecic patch/plaque with multifocal depigmentation, scar-
ring and ulceration at the external vulva and perivulvar skin (case 79).

embedded skin sections in nine of 10 dogs (90%) (Fig-
ure 9). An additional positive LBT for IgA and C3 was
found in three (30%) and two (20%) cases, respectively.
Positive LBTs were detected for four and two immunore-
agents in three (30%) and seven (70%) of 10 dogs,
respectively.
Clinical management and prognosis
Information on treatment outcome was available for all
dogs. Prior to the initial visit, the skin lesions were pre-
sent between three and 24 months, with a median of
approximately 9 months. Drugs prescribed prior to the
diagnosis of GDLE was made included short courses of
antimicrobial drugs (e.g. cefalexin, clindamycin, enrofloxa-
cin; eight of 10 cases, 80%) and a single glucocorticoid
course (four of 10 cases, 40%); these regimens resulted
in only transient improvement of skin lesions in two dogs
(20%). A spontaneous resolution of cutaneous lesions
was not seen in any case. In one dog, an initial
four month combination of doxycycline and niacinamide,
thrice daily at appropriate dosages (250–500 mg per dog
three times daily),21 did not result in clinical improvement.
Once the coexisting SLE was ruled out and the diagno-
sis of GDLE diagnosis had been made, a recommenda-
tion to avoid excessive sun exposure was given to the
owners for all dogs, and three different therapeutic
modalities were initiated: Group 1 (six of 10 dogs; 60%)
was commenced with oral glucocorticoids (1–2 mg/kg/
day, progressively tapered over a month) given with oral
ciclosporin (range 3.3–6 mg/kg, mean 4.8 mg/kg once
daily, Atopica; Elanco Animal Health; Greenfield, IN,
USA), in conjunction with ketoconazole in three dogs

6 © 2016 ESVD and ACVD, Veterinary Dermatology

 Canine generalized discoid lupus

a b

c d

Figure 5. Canine GDLE (a) Hyperpigmented macules and plaques with erythema, adherent scaling, crusting and follicular plugging of the concave
pinnae and caudal (lateral) pinna margin. Note that this this pattern of clinical involvement is highly specific for human discoid lupus erythematosus.
(Case 3). (b) Diffuse hyperpigmentation with adherent scaling on the pinna (Case 5). (c) An unusual pattern of reticulated (net-like) hyperpigmenta-
tion with alopecia on the ventral abdomen. Inset: Higher magnification shows classic “coin-shaped” plaques with central depigmentation, scarring
and peripheral hyperpigmentation (Case 3). (d) Reticulated hyperpigmentation pattern developing from coalescing GDLE skin lesions (Case 2).

(range 1–3.3 mg/kg, mean 2.3 mg/kg once daily; Teva
Pharmaceuticals; Sellersville, PA, USA), Group 2 (three of
10 dogs; 30%) received topical tacrolimus 0.1% ointment
(twice daily, Protopic; Astellas Pharma; Deerfield, IL,
USA) and oral hydroxychloroquine (HCQ) (5 mg/kg once
daily, Gallipot; St Paul, MN, USA); and a single dog (10%)
was started solely on the tetracycline/niacinamide combi-
nation (45 mg/kg of each drug three times a day). A com-
plete remission of clinical signs (scarring alopecia
remained in some lesions) following treatment occurred
after 3–6 months (median 4.5 months) in five dogs (50%;
two dogs each from Group 1 and 2; the dog from Group
3), whereas an approximately 75% partial remission was
seen after 1–6 months (median 5.5 months) in the other
five dogs (50%). An attempt to discontinue or taper the
treatment resulted in the rapid recurrence of typical skin
lesions in six dogs (60%); re-introducing the treatment
modality at lower frequency of administration (e.g. ciclos-
porin every other day; topical tacrolimus twice weekly
without HCQ) maintained remission of clinical signs in
five dogs. In one dog that had several disease flares while
receiving HCQ, oral ciclosporin (5 mg/kg once daily) was
introduced and induced complete clinical remission over
the following four months.
Discussion
Although there are two large case series of dogs with
“classic”, facial (nasal) planum-predominant localized
DLE,10,11 there are three other case reports of dogs with
an apparent generalized variant of this disease.14,16,17
Herein, we describe the signalment, clinical signs and
treatment outcomes of 10 dogs with generalized skin
lesions with clinical, microscopic and immunopathological
features of human GDLE.
Generalized DLE affected various breeds of dogs and
their crosses with an equal representation of male and
female dogs. In humans with GDLE, women are affected
more often than men (female-to-male ratio of 1.5).22 Inter-
estingly, and surprisingly, German shepherd dogs, a

© 2016 ESVD and ACVD, Veterinary Dermatology 7

Banovic et al.
Figure 6. Histopathology of canine GDLE. A marked, subepidermal,
band-like (lichenoid) infiltrate of lymphocytes with fewer plasma cells
is associated with a lymphocytic interface dermatitis reaction. Basal
keratinocyte vacuolation and apoptosis (inset, arrows) are moderate
to marked and are associated with pigmentary incontinence. The
hyperplastic epidermis is multifocally attenuated. Basement mem-
brane zone thickening is present (inset, arrowhead). The middle and
deep dermis have minimal perivascular inflammation. Case 2; haema-
toxylin and eosin, magnification 1009, inset magnification 4009.
Figure 7. Histopathology of canine GDLE. Mild lymphocytic inter-
face dermatitis is associated with multifocal suprabasal keratinocyte
apoptosis (arrows). Case 7; Haematoxylin and eosin, magnification
2009.
breed predisposed to develop several forms of LE, such
as SLE,23–25 localized facial DLE11 and MCLE,13 were not
represented in this population. This discrepancy may be
explained by the German shepherd dog breed not being
predisposed to GDLE, by the small size of our study
group or by a possible clinical misdiagnosis of this disease
as “idiopathic lichenoid dermatoses” based on
histopathological identification of a “lichenoid tissue reac-
tion” in dogs.26 Indeed, one dog from our series had been
initially diagnosed and referred with such a diagnosis. The
age of onset of GDLE was variable, with most dogs
exhibiting their first skin lesions in mid to late adulthood.
A comparable age of onset is reported for humans with
DLE, as the disease most commonly develops in the
fourth to fifth decade.27
As defined by our inclusion criteria (i.e. lesions resem-
bling those of human GDLE), erythematous disc-like pla-
ques with adherent scaling that extended into hair
follicles and dyspigmentation were seen in all of our
cases. The central loss of normal skin texture and scarring
that occurred as the result of long term persistent DLE
activity was present in the centre of skin lesions of all but
one dog. Follicular plugging (i.e. comedones) was a
8 © 2016 ESVD and ACVD, Veterinary Dermatology
prominent feature of canine GDLE, as it is in the human
disease. However, the characteristic “carpet tack” sign
seen in human DLE,6 which are follicular-sized keratotic
spikes similar in appearance to carpet tacks at the under
surface of removed adherent scales, unfortunately was
not assessed in these cases. However, papular, corneo-
cyte-plugged follicles within areas of hyperpigmentation
in the concave pinnae and caudal (lateral) ear margin, a
pattern highly specific for human DLE,6 was also seen in
several of the canine cases. Although any ethnic group
can be affected with human DLE, collective data indicate
that skin lesions with typical inflammatory hypo- and
hyperpigmentation are more frequent in darker-skinned
individuals, whereas in patients with light skin, plaques
usually appear grey or have minimal pigment alteration.6
Interestingly, a diffuse reticulated hyperpigmentation on
the ventral abdomen and lateral thorax was present in
two dogs. Such an unique pigmentation pattern has been
reported in a dog with an alopecic variant of CCLE,15 dogs
with MCLE13 and recently in a dog with a presumptive
idiopathic EM.18
In humans with DLE, discrete plaques can develop on
the nasal, conjunctival and genital mucosa.27,28 Although
four dogs included in the present study exhibited typical
DLE lesions in mucocutaneous regions, most commonly
in the genital/perigenital area, there are important differ-
ences between their character and that of lesions seen in
dogs with MCLE.13 In the latter, characteristic extensive
erosive skin lesions, sometimes with peripheral hyperpig-
mentation, that are restricted to mucocutaneous regions
predominate, but the depigmentation and scarring of
GDLE are typically not seen in these dogs.13 Remarkably,
one dog with GDLE and liver-associated NME developed
classical DLE lesions of depigmentation, erythema, scar-
ring and crusting at perioral, periocular and perianal areas,
long after the development and apparent healing of the
initial NME-associated oedematous and erosive lesions.
The occurrence of DLE lesions in this dog at previous
NME-associated mucocutaneous locations could be evi-
dence suggesting that GDLE lesions, similarly to those of
human DLE, can follow any form of cutaneous trauma, a
response known as the Koebner phenomenon.29
In humans affected with the generalized variant of
DLE, a positive ANA titre is frequently found, and it repre-
sents a risk factor for development of SLE within 5 years
after the initial diagnosis of skin lesions.30 Seven dogs in
this report had a low positive ANA serum titre, but a pro-
gression to the exhibition of additional criteria for SLE
was not seen in any dog within a median follow-up of
2.5 years (range from 0.5 to 6 years). To the best of the
authors’ knowledge, the progression from a CCLE variant
to SLE has been reported only in one dog.15
The histology of DLE in humans is characterized by a
lichenoid interface dermatitis reaction pattern, which was
an inclusion criterion in this study (i.e. cell-rich, lympho-
cytic interface dermatitis).1,2,31,32 Like typical, fully devel-
oped DLE in humans, interface dermatitis occurred in a
hyperplastic epidermis with focal areas of epidermal atro-
phy, epidermal hyperpigmentation or depigmentation,
and pigmentary incontinence.3,32,33 Similarly to human
GDLE, the interface reaction (vacuolar degeneration,
apoptosis and loss of basal cells) was well developed and
 Canine generalized discoid lupus

a b

Figure 8. Histopathology of canine GDLE (a) The deep infundibulum and isthmus of a hair follicle with lymphocytic interface folliculitis and mural
folliculitis associated with perifollicular lymphoplasmacytic inflammation, pigmentary incontinence and mild follicular hyperkeratosis (Case 9). (b) In
this inferior portion of an anagen stage hair follicle, mild lymphocytic mural folliculitis is present in the external root sheath. A few lymphocytes
(arrows) are present in the follicle wall and inflammation in the perifollicular dermis is absent (case 9). (c) A hair follicle unit has marked hair follicle
atrophy (arrows) and a few small islands of external root sheath epithelium contain a few lymphocytes (Case 4). Magnification 1009. Haematoxylin
and eosin.

more severe than is typical of localized DLE in dogs.31,32
As a consequence of this severity, microscopic intrabasal
clefts were observed in two cases. Apoptosis of supraba-
sal keratinocytes occurs in canine13,34 and human
CLE32,35 and was common in our dogs with GDLE. Inter-
face dermatitis and basement membrane thickening
were more prominent than suprabasal apoptosis and
satellitosis; the latter two findings typically are also seen
in the context of EM and toxic epidermal necrolysis.8
Interestingly, occasional foci of grouped suprabasal apop-
tosis, in conjunction with lymphocytic satellitosis, were
observed and mimicked an EM-type reaction pattern18 in
a few skin sections. Similar observations of increased
© 2016 ESVD and ACVD, Veterinary Dermatology
suprabasal apoptosis were identified in association with
skin chronicity in ECLE of German shorthaired pointers,34
and they have been reported for canine localized DLE as
well.31 With the addition of these cases, suprabasal ker-
atinocyte apoptosis is now recognized in several different
forms of CCLE in dogs, including localized DLE,31 GDLE,
MCLE13 and ECLE.34 It should be noted that solar injury is
an additional factor that both exacerbates LE lesions in
dogs and humans,1,2 and sun induced damage could
contribute to the development of apoptosis of suprabasal
keratinocytes.1,2,31,32
Lichenoid inflammation, a subepidermal band of lym-
phocytic infiltration, predominated in our cases with
9
Banovic et al.
a dermatopathy) are necessary to elucidate whether mucin
b atrophy.39 Human DLE is classified as a primary scarring
Figure 9. Direct immunofluorescence of canine GDLE (a) Thick and
patchy IgG deposition along the epidermal basement membrane
zone. (i.e. positive lupus band test; arrowheads). Inset: Magnification
of IgG deposition with fluorescent round cells in the superficial der-
mis that represent IgG-positive plasma cells, a common finding at
inflamed mucocutaneous junctions [Case 2; anti-IgG fluorescein with
diamidino phenylindole (DAPI), 109 magnification]. (b) Thick and pat-
chy IgM deposition along the epidermal basement membrane zone.
(Case 5; anti-IgM fluorescein with DAPI, 109 magnification).
GDLE, and similarly to late stage DLE lesions in humans,3
this band was sometimes greatly diminished in areas of
superficial dermal fibrosis. Additionally, a lichenoid band
was absent in two cases, which is a feature of early DLE
lesions in humans.3 In our dogs, a perivascular pattern of
inflammation was mild superficially and usually absent in
the middle and deep dermis, which is similar to dogs with
localized DLE.31 This is in contrast to humans with local-
ized DLE or GDLE where perivascular inflammation is
often well developed throughout the dermis.3,32
Thickening of the BMZ occurred in 60% of our cases
and this is a characteristic, but not specific, feature of
CCLE in dogs and humans.10–13,31,32 Clinical scarring was
attributed to the superficial dermal fibrosis observed his-
tologically. Increased epidermal and dermal mucin depos-
its have been proposed as an additional diagnostic factor
for localized DLE in the dog;36 however, the detection of
skin mucin deposits alone has limited specificity in
humans and is common in other dermatoses such as EM,
lichen planus and fixed drug reactions.37 Detailed studies
characterizing skin mucin distribution and deposition in
canine CLE variants (localized DLE, GDLE, ECLE, VCLE,
MCLE) and other diseases (EM variants, ischemic
10
deposition in the skin of dogs with CLE is a specific find-
ing and is able to distinguish between different disease
entities. Similarly to human CLE forms, in which
histopathological findings can overlap and may not clearly
differentiate between subtypes,3,38 our study suggest
that biopsy findings alone do not differentiate GDLE from
other forms of canine CCLE (localized DLE, MCLE and
ECLE) or SLE.
Scarring alopecia occurs on the head in localized DLE in
dogs but histological descriptions of follicular changes are
lacking.9–11,31 In humans, when localized DLE involves
the scalp, scarring alopecia is relatively common, occur-
ring in 34% of DLE skin sections in one study; it is associ-
ated with lymphocytic interface folliculitis and follicular
(cicatricial) alopecia because permanent alopecia occurs
clinically and direct lymphocytic targeting of the follicle
(interface folliculitis) is associated with follicular atrophy
and, ultimately, loss of the follicular epithelium – the follic-
ular scarring event.40–42 Concentric laminar fibrosis
occurs around the infundibulum and mid-follicle but it is a
mild, late stage event and is not the main reason for clas-
sification of DLE as a scarring alopecia.40–42 In our study
of canine GDLE, alopecia occurred in nearly all cases and
lymphocytic interface folliculitis involved the infundibulum
and extended into the isthmus as for human DLE.43,44
Lymphocytic mural folliculitis was also common, usually
milder and involved the infundibulum, isthmus and infe-
rior hair follicle segments, typically sparing the bulb. This
mural pattern mirrors that of human DLE, where it is also
called a panfollicular pattern, but it is considered to be
minimal and poorly described.39,43 Follicular atrophy was
present in all cases and ranged from partial to complete.
The combination of lymphocytic interface folliculitis,
advanced follicular atrophy and lack of hair regrowth in a
subset of dogs supports the classification of canine GDLE
as a primary scarring alopecia.41,42 Perifollicular fibrosis
was not a feature in our study, however. Follicular hyperk-
eratosis, plugging and dilation occurred in our cases clini-
cally, as is reported in human DLE, but related histological
changes in follicles were very limited, a clinicopathologi-
cal discrepancy that some authors have noted for human
DLE.32,39 Appropriate biopsy site selection for GDLE
lesions is at the periphery of the lesion, which presum-
ably has less advanced follicular injury than older central
areas, and this could explain the limited infundibular
changes and perifollicular fibrosis histologically in the pre-
sent study. Sebaceous gland atrophy in our cases was
sometimes complete and often mild and partial, which is
similar to descriptions of human DLE, but lacked the mild
glandular lymphocytic infiltrate that can occur.32 In dogs
with ECLE, partial to complete sebaceous gland atrophy
occurs in synchrony with follicular atrophy; it is associated
with a mild lymphocytic periglandular infiltrate, which we
did not see in our cases.12
The LBT initially was considered to be quite specific for
human CLE but controversies regarding terminology
(number of different deposits at dermo-epidermal junc-
tion) and standardization (lesional versus nonlesional skin,
sun exposed versus sun protected skin) have clouded its
diagnostic value.6 A positive LBT in sun protected
© 2016 ESVD and ACVD, Veterinary Dermatology

nonlesional skin appears to have the highest diagnostic
specificity for clinical association with SLE.19 Further-
more, most authors agree that the LBT specificity and
predictive value increases with the number of immunore-
actants detected at the dermal epidermal junction.45,46 In
our series, a linear deposition of IgG and IgM at the
dermo-epidermal basement membrane zone (i.e. a posi-
tive LBT) of lesional skin was found in 90% of cases,
resembling the findings seen in human DLE lesions.45,47
Interestingly, the most commonly detected immunoreac-
tant deposited in facial-predominant canine localized DLE
was C3 (90–100%), whereas IgG and IgM were revealed
in 40–70% of cases, respectively.10,11 These variable
results between canine localized and generalized DLE
could be related to differences in tissue fixation tech-
niques (frozen versus formalin), antigen retrieval methods
and/or immunofluorescence staining protocols. To inves-
tigate the value of performing DIF in canine CLE diagnos-
tic investigation, future studies regarding the sensitivity
and specificity of a positive LBT for the diagnosis of CLE
variants are warranted.
Currently, there are no medications approved specifi-
cally for the treatment of human CLE.48 Besides photo-
protection, glucocorticoids and/or calcineurin inhibitors
remain the classic topical approach for localized DLE,
whereas the systemic drug of choice is the antimalarial
drug HCQ.48 In this report, various treatment regimens
were successfully used to treat dogs with GDLE. Oral
HCQ in conjunction with topical tacrolimus application
helped to induce and maintain remission of skin lesions in
two dogs with this disease. Although retinal toxicity limits
the use of HCQ in humans, it was not observed in any
dog in this case series or in dogs with ECLE.34,49 In our
study, a remarkable improvement or a complete remis-
sion in GDLE skin lesions followed treatment with ciclos-
porin along with a short course of glucocorticoids at its
onset. Given that ciclosporin and tacrolimus share a simi-
lar mechanism of action on T-lymphocytes, and that tacro-
limus ointment has been used successfully for topical
treatment of human47 and canine localized DLE,50,51 we
had inferred that ciclosporin might be beneficial for treat-
ment of canine GDLE. Interestingly, ciclosporin is no
longer recommended for treatment of human CLE due to
a relatively unfavourable risk–benefit profile.48
Since 1992, antibiotics of the tetracycline family along
with niacinamide have been suggested to be beneficial
for treatment of canine immune-mediated skin diseases,
including the CLE variants; localized DLE,20,52 ECLE52 and
MCLE.13,52 In our case series, one dog did not respond to
a 4 month combination of doxycycline and niacinamide,
whereas another dog had a complete remission of signs
with tetracycline and niacinamide. In humans, evidence
exists on the equipotency of different tetracycline for
therapy of bullous pemphigoid,53 as some authors suc-
cessfully used doxycycline or minocycline as an alterna-
tive to tetracycline. Although tetracycline and doxycycline
were shown to be relatively similar in effectiveness to
treat canine lupoid onychodystrophy (idiopathic onychitis/
onychomadesis),54 there are no data on which of the
tetracyclines is more effective, and whether niacinamide
is of synergistic value for treatment of CLE variants in
dogs; this needs to be studied further.
© 2016 ESVD and ACVD, Veterinary Dermatology
Canine generalized discoid lupus
In conclusion, we report herein 10 dogs with an unique
clinical phenotype as well as histological and immunofluo-
rescence findings that resemble the features of general-
ized human DLE patients. Skin lesions of canine GDLE
appear to respond to a wide range of treatments, but half
of the cases experienced relapses upon the tapering of
drug dosages. Our limited outcome data suggest that
ciclosporin should be considered as a potentially effective
therapeutic option for canine GDLE, especially for dogs
refractory to HCQ, niacinamide and tetracycline therapy.
Acknowledgments
The authors thank Fiona Lee, Ryan Hospital, University of
Pennsylvania School of Veterinary Medicine, for sharing
clinical information on Case 4.
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Re
sume

Contexte – Le lupus e
rythe

mateux disco€ıde ge
ne

ralise

(GDLE) est un variant canin nouvellement reconnu
du lupus cutane
chronique (CLE) qui n’est pas bien de
fini.
Hypothe ses/Objectifs – Nous rapportons ici le signalement, les signes cliniques, l’efficacite
ments, l’histopathologie et les donne
es immunologiques de 10 chiens atteints de GDLE.
Me
thodes – Les crite
res d’inclusion e
taient (i) a>3 mois de comme
lise
es correspondant a une atteinte chronique ou re
cidivante; (ii) des le
de la GDLE de l’homme; (iii) l’histopathologie de CLE (dermatite d’interface riche en lymphocytes). L’immu-

rologie anticorps antinucle
nofluorescence directe (IF) et la se
12
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584.
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and normal skin. J Cutan Pathol 2015; 42: 722–729.
38. Sontheimer RD. Lichenoid tissue reaction/interface dermatitis:
clinical and histological perspectives. J Invest Dermatol 2009;
129: 1088–1099.
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lupus erythematosus. Br J Dermatol 1992; 126: 307–314.
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103–110.
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46. Crowson AN, Magro CM. Cutaneous histopathology of lupus
erythematosus. Diagn Histopathol 2009; 15: 157–185.
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479–482.
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and treatment. Best Pract Res Clin Rheumatol 2013; 27: 391–
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trial and pharmacodynamic evaluation of combination hydroxy-
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0.1% tacrolimus for the treatment of discoid lupus erythemato-
sus and pemphigus erythematosus in dogs. J Am Anim Hosp
Assoc 2004; 40: 29–41.
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blinded placebo controlled cross-over study evaluating 0.03%
tacrolimus ointment monotherapy in the treatment of discoid
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188.
52. Adolph ER, Scott DW, Miller WH et al. Efficacy of tetracycline
and niacinamide for the treatment of cutaneous lupus erythe-
matosus in 17 dogs (1997–2011). Jpn J Vet Dermatol 2014; 20:
9–15.
53. Loo WJ, Kirtschig G, Wojnarowska F. Minocycline as a therapeu-
tic option in bullous pemphigoid. Clin Exp Dermatol 2001; 26:
376–379.
54. Mueller RS, Rosychuk RA, Jonas LD. A retrospective study
regarding the treatment of lupoid onychodystrophy in 30 dogs
and literature review. J Am Anim Hosp Assoc 2003; 39: 139–
150.

des traite-

moratifs de le
sions cutane
es ge

ne

ra-

sions cutane
es ressemblant  a celles

aires ont e
te

e
tudie

es si possible.
© 2016 ESVD and ACVD, Veterinary Dermatology
 Canine generalized discoid lupus

Re
sultats – Des races varie
es ont e
te

atteintes 
a l’^
age adulte 
a adulte-avance
. Les crite
res de se
lection
des plaques annulaires (« disco€ıdes) a polycycliques multifocales ge
ne
ralise

es avec modification de pig-
mentation, marges e
rythe

mateuses, squames adhe
rentes, obstruction folliculaire et alope
cie centrale ont

te
e
observe
s chez tous les chiens. Pour neuf chiens, les plaques contenaient un squamosis central faible  a
mode
re

avec de
pigmentation et/ou hyperpigmentation. Pour aucun chien il n’y a eu de progression de la
maladie en lupus e
rythe

mateux syste
mique sur une pe
riode moyenne de suivi de 2.5 ans. Par les crite res
d’inclusion, la dermatite d’interface avec e
paississement de la zone de la membrane basale (BMZ), de
l’apoptose suprabasale et/ou une fibrose dermique e
taient observe
s chez certains chiens. Une folliculite
d’interface infundibulaire e
tait fre

quente; celle-ci e

voluait parfois en folliculite murale dans les portions bas-
ses des follicules et se de
veloppait en association avec une atrophie folliculaire ou se
bace
e. L’IF directe
re
ve

lait une disposition en patch d’immunoglobuline IgG et IgM sur la BMZ. Les le
sions re

pondaient  a une
varie
te

de traitements, comprenant la ciclosporine, l’hydroxychloroquine, la tacrolimus topique et la te
tracy-
cline/niacinamide. Les re
cidives e
taient fre

quentes apre s diminution de doses des traitements.
Conclusions et importance clinique – Ces observations supportent l’existence d’un homologue canin du
GDLE de l’homme.

Resumen
Introduccio
n – el lupus eritematoso discoide generalizado (GDLE) es una variante recientemente recono-
cida de lupus eritematoso cut
aneo cro
nico canino (CLE) que no est
a bien caracterizada.
Hipo
tesis/Objetivos – en este art
ıculo se presenta la anamnesis, signos cl
ınicos, resultados del tratamien-
to, histopatolog
ıa y hallazgos inmunolo
gicos de 10 perros con GDLE.
Me
todos – Los criterios de inclusio
n fueron: (i) una historia> 3 meses de lesiones cut
aneas generalizadas
que indicaban una naturaleza cro
nica o recurrente; (ii) lesiones de la piel similares a las de GDLE humana;
(iii) histopatolog
ıa de CLE (dermatitis de interfase rica en linfocitos). Se investigaron por inmunofluorescen-
cia directa (IF) y serolog
ıa los anticuerpos antinucleares siempre que fue posible.
Resultados – Diversas razas fueron afectadas con perros de mediana a avanzada edad. Criterios de
seleccio
n presentes en todos los perros fueron la presencia de lesiones multifocales, anulares (“discoi-
des”) a placas polic
ıclicas con cambios en la pigmentacio
n, margen eritematoso, costras adherentes, tapo-
namiento folicular y alopecia central. En nueve perros, las placas conten
ıan leve a moderada cicatrizacio
n
central con depigmentacio
n y / o hiperpigmentacio
n. No hubo perros en los que la enfermedad progresara
a lupus eritematoso siste
mico con un tiempo medio de de seguimiento de 2,5 an ~os. Por los criterios de
inclusio
n, hubo dermatitis de interfase con engrosamiento de la membrana basal (BMZ), apoptosis supra-
basal y / o fibrosis de
rmica en algunos perros. La inflamacio
n de interfase infundibular fue comu
n y a veces
progresaba a foliculitis mural en los segmentos ma
s bajos del fol
ıculo, y se produc
ıa con atrofia de las
gl
andulas seb
aceas y foliculos. El IF directa revelo
deposicio
n irregular de inmunoglobulina IgG e IgM en la
BMZ. Las lesiones respondieron a una variedad de tratamientos, incluyendo ciclosporina, hidroxicloroquina,
tacrolimus y tetraciclina / niacinamida. Las reca
ıdas fueron frecuentes con la disminucio
n de la dosis de
medicamentos.
Conclusiones e importancia cl
ınica – Estas observaciones confirman la existencia de un homo
logo
canino de GDLE humana.

Zusammenfassung
Hintergrund – Der generalisierte Diskoide Lupus Erythematosus (GDLE) ist eine neu erkannte canine Vari-
ante des chronischen kutanen Lupus Erythematosus (CLE), der noch nicht gut beschrieben wurde.
Hypothese/Ziel – Wir berichten hiermit vom Signalement, den klinischen Zeichen, dem Behandlungser-
folg, der Histopathologie und den immunologischen Befunden von 10 Hunden mit GDLE.
Methoden – Inklusionskriterien waren: (i) a > 3 monatiger Vorbericht einer generalisierten Hautver€ ande-
rung, die auf eine chronische oder wiederkehrende Natur schließen l€ asst; (ii) Hautver€anderungen, die jenen
der Menschen mit GDLE €ahneln; (iii) eine mit CLE kompatible Histopathologie (Lymphozyten-reiche Inter-
face Dermatitis). Direkte Immunfluoreszenz (IF) und Antiko €rperserologie wurden wenn mo €glich unter-
sucht.
Ergebnisse – Verschiedene Rassen waren im mittleren bis ho €herem Alter betroffen. Die Auswahlkriterien
von generalisierten multifokalen, annularen bis polycyclischen Plaques mit Pigmentver€ anderungen, erythe-
mato €sen R€andern, anhaftenden Schuppen, follicul€arem Plugging und einer zentralen Alopezie wurden bei
allen Hunden gefunden. Bei neun Hunden enthielten die Plaques milde bis moderate zentrale Narben mit
einer Depigmentierung und/oder Hyperpigmentierung. Es gab keine Hunde bei denen sich die Krankheit
innerhalb von einem medianen Follow-up von 2,5 Jahren zu einem systemischen Lupus Erythematosus
weiterentwickelte. Nach den Aufnahmekriterien trat die Interface Dermatitis gemeinsam mit einer Verdi-
ckung der Basalmembran (BMZ), einer suprabasalen Apoptose und/oder einer dermalen Fibrose bei eini-
gen Hunden auf. Eine Interface Dermatitis des Infundibulums war h€ aufig; diese entwickelte sich
gelegentlich in den unteren Follikelabschnitten zu einer muralen Follikulitis, gleichzeitig trat sie mit einer fol-
likul€aren und sebazio €sen Dru €senatrophie auf. Die direkte IF zeigte fleckige Ablagerungen von
© 2016 ESVD and ACVD, Veterinary Dermatology 13
Banovic et al.

Immunglobulin IgG und IgM an der BMZ. Die Vera €nderungen wurden auf eine Reihe von Behandlungen
besser; diese bestanden aus Ciclosporin, Hydroxychloroquinolon, topischem Takrolimus und Tetrazykline/
Niacinamid. Sobald die Medikamente ausgeschlichen wurden, war ein Wiederauftreten h€aufig.
Schlussfolgerungen und klinische Bedeutung – Diese Beobachtungen unterstu €tzen die Tatsache, dass
ein canines Homolog zum humanen GDLE existiert.

要約
背景 – 全身性円板状紅斑性狼瘡(GDLE)は、慢性皮膚紅斑性狼瘡(CLE)の犬の1亜型として新たに認知されている
が、その特徴はよくわかっていない。
仮説/目的 – 10頭のGDLEの犬における、シグナルメント、臨床所見、治療反応性、病理学的所見および免疫学
的所見をここに報告する。
方法 – 組み入れ基準は以下のものとした:(i)3ヶ月以上の慢性あるいは再発性の全身性皮膚病変を持つこと; (ii)皮膚
病変が人のGDLEと類似していること; (iii)病理組織学的にCLE(リンパ球を主体とする境界部皮膚炎)の所見を持つこ
と。直接免疫蛍光染色(IF)および抗核抗体血清検査は可能な限り実施した。
結果 – 中年齢から高齢の様々な犬種が罹患していた。組み入れ基準である、全身多発性の環状(”円板状”)から
多環状の色素変化を伴う局面、紅斑性の縁、固着性の鱗屑、毛嚢性栓および中心性の脱毛が、全ての症例で
認められた。9頭では、局面は色素脱失および/あるいは色素沈着を伴う軽度から中程度の中心性の瘢痕を伴ってい
た。中央値2.5年の追跡調査の間に、全身性エリテマトーデスに進行した症例はいなかった。組み入れ基準である境
界部皮膚炎は、表皮基底膜領域(BMZ)の肥厚、基底層上細胞のアポトーシスおよび/あるいは真皮の線維化をいく
つかの症例で伴っていた。毛漏斗部の境界部毛包炎が一般的に認められ、時折、毛包下部の壁内毛包炎へと移
行し、毛包および皮脂腺の萎縮を伴っていた。直接IFでは、免疫グロブリンIgGおよびIgMの斑状の沈着がBMZに
認められた。病変は、シクロスポリン、ヒドロキシクロロン、タクロリムス塗布、テトラサイクリン/ナイアシンアミドなどの様々
な治療に反応した。薬剤を漸減するとほとんどの症例で再発した。
結論および臨床的な重要性 – これらの所見は、人のGDLEに相同する犬の疾患の存在を支持するものである。

摘要
背景 – 泛发性盘状红斑狼疮(GDLE),最近被认为是犬慢性皮肤型红斑狼疮(CLE)的一种变异,目前未能对其充
分定义。
假设/目的 – 本文报道了10只GDLE患犬的病征、临床症状、治疗效果、组织病理学和免疫学发现。
方法 – 入选标准为:(i)慢性或复发性全身性皮肤病,病史超过3个月;(ii)皮肤病变类似于人类GDLE;(iii) CLE(淋
巴细胞丰富的界面皮炎)组织病理学特征。尽可能通过直接免疫荧光法(IF)和抗核抗体血清学检查。
结果 – 患犬为不同品种、成年中期至后期。所有犬表现为全身多灶性、环状(盘状)或多环状斑块,伴随色素
改变、边缘红斑、粘附皮屑、毛囊角栓和中心脱毛。9只犬的斑块伴有轻度或中度色素减退和/或色素过度
沉着。在中值回访时间2.5年内,没有犬发展为全身性红斑狼疮。每一个入选病例均伴有基底膜区(BMZ)增
厚、基底上层细胞凋亡和/或部分犬皮肤纤维化。常见漏斗区的界面毛囊炎;有时可能在毛囊末端发展为毛
囊壁炎,同时伴有毛囊和皮脂腺的萎缩。直接IF显示,BMZ的免疫球蛋白IgG和IgM缀块性沉积。多种治疗对
病变有效,包括环孢素、羟化氯喹、外用他克莫斯和四环素/烟酰胺。药物逐渐减量后常见复发。
总结和临床意义 – 这些发现表明,存在与人类GDLE同源的犬GDLE。

Resumo
Contexto – Lu
pus eritematoso discoide generalizado (LEDG) e
uma variante canina do lu
pus eritematoso
cut^aneo cro ^nico (LECC) reconhecida recentemente e pouco caracterizada.
Hipo
tese/Objetivos – Relatar os sinais cl
ınicos, tratamentos empregados, histopatologia e achados imu-
nolo
gicos de dez c~aes com LEDG.
Me
todos – Os crite
rios de inclus~ao foram: (i) histo

rico de leso
~es cut^aneas generalizados por tre ^s ou mais
meses, indicando natureza cro ^nica ou recorrente; (ii) leso
~es cut^
aneas semelhantes  as do LEDG humano;
(iii) histopatologia sugestiva de LECC (dermatite de interface com infiltrado linfocit
ario). Imunofluoresce^ncia
direta (IFD) e sorologia para anticorpo antinuclear foram investigadas sempre que poss
ıvel.
Resultados – Diversas racßas foram afetadas em uma faixa et
aria me
dia entre a metade ao fim da vida
adulta. O crite
rio de selecß~ao de leso
~es anulares (“discoide”) a placas polic
ıclicas com alteracßo~es pigmenta-
res , margem eritematosa, escamas aderidas, cilindros foliculares e alopecia central foram observados em
todos os c~aes. Em nove, as placas apresentavam
area cicatricial central discreta a moderada com despig-
mentacß~ao e/ou hiperpigmentacß~ao. Nenhum dos c~ aes apresentou progress~ ao para lu
pus eritematoso
siste ^mico em dois anos e meio, em me
dia, de acompanhamento. Por crite
rio de inclus~ ao, dermatite de
interface ocorreu com espessamento da membrana basal (MB), apoptose suprabasal e/ou fibrose de
rmica,
em alguns animais. Foliculite de interface foi comum, esta algumas vezes evoluiu para foliculite mural em
segmentos foliculares profundos, e ocorreu com atrofia folicular e de gl^ andulas seb
aceas. IFD revelou
deposicß~ao irregular de imunoglobulina do tipo IgG e IgM na MB. As leso ~es responderam positivamente a
diversos tratamentos, incluindo ciclosporina, hidroxicloroquina, tacrolimus to
pico e tetraciclina com niacina-
mida. Recidivas foram comuns apo
s a descontinuacß~ao da medicacß~ao.
Concluso ~ es – Estas observacßo ~es suportam a existe ^ncia da forma homo
loga canina de LDG humana.

14 © 2016 ESVD and ACVD, Veterinary Dermatology