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Abstract The clinical, histopathologic and immunopathologic features of a novel form of isthmus mural
folliculitis in dogs, which resembles pseudopelade in humans, were characterized. Clinically, dogs exhibited
variably distributed foci of alopecia that persisted without treatment or did not respond to
immunosuppressive therapy. Histopathologically, mixed mononuclear cell inltrates, largely lymphocytes,
inltrated the follicular isthmus. Occasionally, inammation extended above and below the follicular isthmus
but did not involve the hair bulb or the epidermis. Severe follicular atrophy and variable atrophy of sebaceous
glands occurred in all dogs. Folliculotropic lymphocytes exhibited most commonly CD3 and CD8 (cytotoxic
T cells). Autoantibodies specic for the lower hair follicle were detected in the serum of aected patients.
Western immunoblotting demonstrated binding of these antibodies to multiple follicular keratinocyte
proteins, including hair keratins and trichohyalin. Lack of hair regrowth (in contrast to canine alopecia
areata), as well as location of inammation and extreme atrophy of adnexal units are similar to ndings seen
in human pseudopelade.
Ahed
Bhed
Ched
Keywords: alopecia, dog, mural folliculitis, pseudopelade.
Dhed
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ndings of this novel form of mural folliculitis in
INTRODUCTION
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ve dogs.
Mural folliculitis is a histopathologic pattern of
inammation, aecting the follicular wall, that has
CASE SUMMARIES
been reported recently in dogs and cats.1,2 Several
histopathologic subtypes have been described, inFive dogs developed patchy alopecia that was
cluding interface, inltrative, pustular, and necrotizclinically noninamed, and usually accompanied by
ing.1 Inltrative mural folliculitis is characterized by
ne scale. Dog 1, a 2-year-old, castrated male
inammation of the outer root sheath which centres
German Shepherd dog, presented with multiple,
predominantly on the follicular isthmus. Inammasmall (24 cm) foci of alopecia, developing rst on
tion may extend above and below this level, but
the chin and base of the right ear, and subsequently
spares the follicular bulb.
spreading to the left ear. Skin scrapings and a
Pseudopelade of Brocq is an alopecic disorder of
dermatophyte culture were negative. The lesions
humans that is characterized, histologically, by severe
remained static and did not change over a period of
follicular atrophy and variable inammation. Clini8 months; no therapy was given. Dog 2, a 1-year-old,
cally, the alopecic skin is smooth and noninamed;
spayed female Maltese, developed diuse alopecia
the hair loss is permanent.3,4 Recently, a unique form
over 75% of the body, sparing the head and feet
of inltrative mural folliculitis, leading to severe
(Fig. 1). Skin scrapings and a dermatophyte culture
follicular atrophy, and resembling pseudopelade of
were negative. Based on initial biopsy results, an
humans, has been observed in dogs. A similar entity
autoimmune mechanism was suspected for the hair
also has been observed in a cat; cytotoxic T cells were
loss. However, alopecia persisted over the next 6
demonstrated targeting the follicular isthmus (H.
months despite immunosuppressive therapy with
Power, T. Olivry et al., unpublished observations).
corticosteroids and chlorambucil. Dog 3, a 1-yearThe purpose of this study was to characterize the
old, spayed female Border Collie, had an irregular
clinical, histomorphologic and immunopathologic
focus of alopecia on the shoulder accompanied by
hyperpigmentation and mild scaling. The lesion
measured 6 6 8 cm and slowly expanded over the
Correspondence: T. L. Gross.
Reprint requests to: T. Olivry.
next 15 months (Figs 2 and 3). Skin scrapings and a
# 2000 Blackwell Science Ltd
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RESULTS
Histopathologically, lesional skin biopsy specimens
obtained from all dogs demonstrated similar features.
There was variably intense, often tightly focused
inammation of the follicular isthmus (Fig. 5).
Inammation also extended to the perifollicular
dermis at that level. The folliculotropic inammation
was not uniform and had a tendency to skip some
follicular units (Fig. 6). In most cases, lymphocytes
predominated and fewer histiocytes/dendritic cells
were observed. Apoptosis of follicular epithelial cells
was not observed. Plasma cells were seen in three of
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Pseudopelade in dogs
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Figure
6.
The
folliculotropic
inammation is aecting one follicle
within the unit; the adjacent follicles are
spared;
dog
3
(H&E;
original
magnication 625).
served in conjunction with demodicosis and dermatophytosis in dogs.1,7 These agents were not demonstrated in the ve dogs of this study. Isthmus mural
folliculitis may be a feature of sebaceous adenitis;1
although sebaceous glands were frequently absent in
areas of severe follicular atrophy in the dogs of this
report, they often were spared, even in foci of severe
follicular attenuation.
Distinctive clinical features included patchy and
grossly noninamed alopecia which persisted over a
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Pseudopelade in dogs
21
Figure
10.
Immunostaining
using
anticanine CD8 monoclonal antibody;
intrafollicular lymphocytes are cytotoxic
T cells (CD8+); dog 1 (original
magnication 680).
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pseudopelade of humans.3,4 Originally named `pseudopelade of Brocq' after the author of its original
description in 1885, pseudopelade has been classied
as a `scarring' alopecia because hair loss is permanent.8
As scarring implies localized, nonspecic destruction
by a pre-existent disease or process, atrophy rather
than true scarring better characterizes the prominent
histopathologic feature of pseudopelade.3,9 Scarring
was not observed in the dogs of our study. Although
most reports of human pseudopelade describe mild to
absent inammation,3,4,9 early lesions demonstrate
dense accumulations of lymphocytes in and around
the upper hair follicle.8,10 Lymphocyte-associated
apoptosis has been described in human pseudopelade,10 but was not observed in the dogs of this study.
Histological dierences between the isthmus mural
folliculitis of the dogs of this report and pseudopelade
of humans include more transient inammation that is
less inltrative to the follicular wall in humans.
# 2000 Blackwell Science Ltd, Veterinary Dermatology, 11, 1724
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Dog 1
Dog 2
Dog 3
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Pseudopelade in dogs
eases.5,6 The autoantibody response appears to be
more heterogeneous in canine pseudopelade (Table 1)
than in alopecia areata in which antibody production
to trichokeratins predominates.6 The presence of
follicular autoantibodies may represent a nonspecic
epiphenomenon that results from exposure of follicular antigens due to folliculocentric inammation of
any cause. Immunologic studies in dogs with other
forms of folliculitis are required to determine the
specicity of follicular autoantibody formation.
Although autoantibodies to follicular antigens
occur in both pseudopelade and alopecia areata in
dogs, the level of lymphocyte homing to the hair
follicle is dierent. Thus, antigen-specic cytotoxic Tcell damage may be the initiating event. A central role
for cytotoxic T cells also has been demonstrated in
human alopecia areata.14,15 Detailed immunological
studies have not been performed for pseudopelade in
humans; a previous report proposed lymphocytemediated apoptosis as a mechanism for the alopecia.10
Apoptosis was not observed in the dogs of this report.
A cause for the variability of the clinical distribution of alopecic lesions in the dogs of this study was
not determined. In humans, permanent alopecia may
be an endpoint for various immunological triggers,
including lichen planopilaris and discoid lupus
erythematosus.3 It is possible that dierent immunological events may initiate this form of mural
folliculitis in dogs. Dog 3 was of particular interest
in that lesions occurred over the shoulder, a common
site for vaccination in animals. One of the authors
(T.L.G.) has seen isthmus mural folliculitis in a cat
with a similar clinical distribution.
In conclusion, this distinctive form of isthmus
mural folliculitis in dogs is probably immunological
in origin and leads to apparently permanent hair loss
that fails to respond to immunosuppressive therapy.
Further studies are needed to elucidate the immunological sequence of events and their roles in the
pathogenesis of this condition.
ACKNOWLEDGEMENTS
The authors would like to thank Drs Rainee Johnson,
Mitchell Song, Helen Power, Caroline de Jaham, and
Marianne Heimann for clinical case material, as well
as clinical photographs (Song, Power and de Jaham).
We are also grateful to Dr Peter F. Moore for
providing the monoclonal antibodies specic for
canine leucocyte antigens.
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REFERENCES
1. Gross, T.L., Stannard, A.A., Yager, J.A. An
anatomical classication of folliculitis. Veterinary
Dermatology 1997; 8: 14756.
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