Abstract Recurrent or persistent follicular dysplasia and interface dermatitis are described in nine Boxers. Data
on age, sex, seasonality of alopecia and histopathological features of the follicular dysplasia in these nine Boxers
are comparable with those described in previous reports. The interface dermatitis was characterized by multifocal
annular crusted lesions confined to the areas of follicular dysplasia. The inflammatory lesions were neither pruritic nor painful and affected dogs were otherwise healthy. Histopathologically the clinically inflammatory lesions
were characterized as an interface dermatitis. Immunohistochemical studies failed to demonstrate immunoglobulins or complement at the basement membrane zone or within blood vessel walls. In dogs with recurrent or persistent disease, the follicular dysplasia and interface dermatitis ran identical, concurrent courses of spontaneous
remission and recurrence, or persistence, respectively. One dog with persistent disease was treated successfully
with tetracycline and niacinamide for the interface dermatitis, and melatonin for the follicular dysplasia.
Although the aetiopathogenesis of this newly described condition and the relationship between the two histological reaction patterns are not known, photoperiod and genetic predisposition appear to play a role.
Keywords: Boxer, dog, follicular dysplasia, interface dermatitis.
INTRODUCTION
Follicular dysplasia is well-recognized in the Boxer.16
A more-or-less bilaterally symmetric, well-circumscribed
alopecia and hyperpigmentation are seen, especially
over the flank region. In most cases, the condition is
seasonal and recurrent.
We recently recognized an interface dermatitis
occurring within the areas of follicular dysplasia in
nine Boxers. The purpose of this study is to report the
clinical, histopathological and immunopathological
features of this newly recognized interface dermatitis in
Boxers with recurrent (seasonal) and persistent (nonseasonal) follicular dysplasia.
Histopathological studies
All skin biopsy specimens had been taken with a 6-mm
punch biopsy instrument, fixed in 10% buffered formalin, routinely processed and embedded in paraffin.
Four-micrometre sections had been cut and stained
with haematoxylin and eosin (H&E) and acidorcein
Giemsa (AOG). All biopsy specimens (the original
slides) were systematically reviewed using a standardized histopathological evaluation form (Fig. 1).
A grading system was used to evaluate the severity
of the hair follicle dysplasia.3 Dysplastic hair follicles
were identified as primary hair follicles wherein the
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M. A. Rachid et al.
with 0.5% hydrogen peroxide in methanol. The sections were then rinsed with 70% ethanol followed by
Brij detergent in phosphate-buffered saline (BrijPBS).
Antigenic sites were recovered by digestion with pepsin
for 30 min at 37 C. The sections were then rinsed in
BrijPBS, and blocked with 10% normal goat serum
in PBS. Sections were incubated with rabbit antibody (0.55.0 g mL1; Zymed Laboratories, Inc., San
Francisco, CA, USA) specific for canine immunoglobulin A (IgA), IgG, IgM or complement (C3) for 1 h at
37 C and rinsed with BrijPBS. Negative control sections were treated with nonimmune rabbit serum (1:50
dilution) in similar fashion. Biotinylated antirabbit
secondary antibody (Zymed Laboratories, Inc.) was
applied for 15 min at room temperature, rinsed with
BrijPBS, and followed by streptavidinhorseradish
peroxidase conjugate (Zymed Laboratories, Inc.)
according to the manufacturers instructions. Diaminobenzadine (DAB) chromagen was diluted 1:50 in
0.1 TrisHCl containing 0.01% hydrogen peroxide,
immediately applied to the sections for 15 s, and
rinsed off with distilled water. Sections were then
counter-stained with Azure B, dehydrated and coverslipped with Permount mounting medium. The locations of positively staining cells and skin structures
in sections from nine cases meeting the selection
criteria and from three randomly chosen dogs with
Table 1. Clinical, laboratory tests, and therapeutic information on nine Boxers with concurrent follicular dysplasia and interface dermatitis
Seasonality
Laboratory tests
Previous therapy
4.5
FS
Unknown
9.5
MC
October to April
FS
2.5
January to May
Haemogram, urinalysis,
serum total thyroxine,
skin scrapings
Serum total thyroxine, serum
thyrotropin, antinuclear antibody
Woods light, skin
scrapings, fungal culture
MC
2.5
January to May
MC
Persistent
MC
December to April
February to June
None
March to August
None
None
FS
November to April
None
Cephalexin orally
Case*
1
Sulfadimethoxine-ormetoprim,
cephalexin, and methylprednisolone
orally; benzoyl peroxide shampoo
Sulfadimethoxine-ormetoprim,
cephalexin, and methylprednisolone
orally; benzoyl peroxide shampoo
Cephalexin orally; novel
protein diet
Cephalexin orally
Subsequent therapy
and follow-up
None; owners
moved to
Puerto Rico
None; spontaneous
remission
None; spontaneous
remission
None; spontaneous
remission
Tetracycline and
niacinamide orally
resolved dermatitis;**
melatonin orally
resolved alopecia
None; spontaneous
remission
None; spontaneous
remission
None; spontaneous
remission
None; spontaneous
remission
161
Sex
Duration of disease
(months) prior
to biopsy
Age
(years)
162
M. A. Rachid et al.
Table 2. Immunohistochemical findings in skin biopsy specimens from nine Boxers with interface dermatitis and three dogs with inflammatory
skin disease
Cell staining in the epidermis
ECM staining
Vessel staining
Case No.
IgA
IgG
IgM
C
IgA IgG IgM
C
IgA
IgG
IgM
C
IgA IgG IgM C
Boxers
1
W+ W+
+
W+
WP+
+
W+ +
+
+
+
W+
W+
W+ +
+
W+
3
W+ +
+
4
ND
W+ +
ND W+
W+
ND W+ +
+
ND
5
W+ W+ W+
WP+ +
WP+
+
+
+
W+
6
W+ +
W+
+
+
+
+
+
+
+
7
W+ +
W+
WP+
+
W+
8
W+
+
+
+
+
+
W+
+
+
+
+
W+
Inflamed dog skin
Atopy
+
+
W+
ND
+
+
W+
ND +
+
W+
ND +
+
+
ND
Bacterial pyoderma
+
+
+
Atopy
+
+
W+
+
*Lymphocytes and plasma cells.
ECM, extracellular matrix; ND, not done; W+, weak positive defined as < 20 cells/section, or light staining of the ECM or vessels; WP+, weak/
patchy staining of the ECM.
The uniformly negative epidermal staining does not include stratum corneum where anti-Ig antibodies reacted nonspecifically in every case.
ECM staining was in the interstitium of the superficial dermis, but not the basement membrane zone. Interpreted as leakage from vessels in
inflamed areas.
Vessel staining was in the lumen and on the endothelium, but not the vessel wall.
RESULTS
Nine Boxers with concurrent follicular dysplasia and
interface dermatitis were identified. Three of these nine
dogs were identified in the retrospective histopathological study and had biopsies performed in 2000 (case 6),
1998 (case 7) and 1991 (case 9). Clinical information on
the dogs is presented in Table 1.
Typically, the owners recognized the simultaneous
onset of the noninflammatory alopecia and hyperpigmentation and the multifocal inflammatory lesions.
The earliest inflammatory lesions were variously
described as resembling bumps (papules), bites
(papules), pustules or blisters (vesicles). The inflammatory lesions occurred only within the areas of typical follicular dysplasia (Figs 2 and 3). When the dogs
were examined by veterinarians, papules, pustules and
vesicles were no longer present. Veterinarians observed
inflammatory lesions that were multiple, more-or-less
bilaterally symmetric, well-circumscribed, annular, 2
15 mm in diameter, raised, crusted, scaly, alopecic and
hyperpigmented. They were neither pruritic nor painful, and the dogs were otherwise healthy.
There was no consistent relationship between the
onset of the dermatitis and previous vaccination, drug
therapy or heartworm preventives. Routine laboratory
tests were performed on many of the dogs (Table 1),
and were negative or within normal limits. Five of the
patients had been acquired from shelters within the last
one to three years, and previous medical history was
not available. Only two of the dogs (siblings) were
known to be related. These two dogs lived in the same
Figure 2. Case 2. Note the annular crusts within the area of wellcircumscribed alopecia and hyperpigmentation on the right lateral
trunk of the dog.
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M. A. Rachid et al.
DISCUSSION
Although follicular dysplasia is well-recognized in
Boxers, the cause is unknown. Affected dogs typically
have no associated hormonal imbalance.1,5,6,8,9 Because
most of the dogs experience recurrent, seasonal hair
loss, it has been suggested that photoperiod working
through pineal levels of melatonin and pituitary levels
of prolactin may be involved.46 In fact, typical clinical
and histological findings were reproduced in one Boxer
by keeping it in a dark room for one month during the
summer.10 Lastly, because the disorder is seen with
such frequency in Boxers, a genetic or breed predisposition probably plays a role.26
To our knowledge, the interface dermatitis associated with recurrent and persistent follicular dysplasia
in Boxers reported herein has not been described
previously. We recognized our first clinical case at the
CUHA in January 2001, and had examined or received
biopsy specimens on another five dogs by the end of
the year. Our retrospective histopathological study
revealed that biopsy specimens from three other cases
had been received between 1991 and 2000, but not
165
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and Airedale Terriers: 24 cases (198592). Journal of the
American Veterinary Medical Association 1993; 11: 156772.
3. Rothstein, E., Scott, D.W., Miller, W.H. Jr. et al. A retrospective study of dysplastic hair follicles and abnormal melanization in dogs with follicular dysplasia syndromes or endocrine
skin disease. Veterinary Dermatology 1998; 9: 23541.
4. Guagure, E. Les alopcies dorigine gntique chez le
chien. Point Vtrinaire 1996; 28: 5438.
5. Paradis, M. Alopcies acquises chez le chien. Mdecin
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6. Scott, D.W., Miller, W.H. Jr, Griffin, C.E. Muller and
Kirks Small Animal Dermatology, 6th edn. W.B. Saunders, Philadelphia, 2001.
7. Mauldin, E.A., Scott, D.W., Miller, W.H. et al. Malassezia dermatitis in the dog: a retrospective histopathological and immunopathological study of 86 cases
(199095). Veterinary Dermatology 1997; 8: 191202.
8. Curtis, C.F., Evans, H., Lloyd, D.H. Investigation of the
reproductive and growth hormone status of dogs affected
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9. Daminet, S., Paradis, M. Evaluation of thyroid function
in dogs suffering from recurrent flank alopecia. Canadian
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10. Ando, J., Nagata, M. Seasonal flank alopecia in a Boxer.
Japanese Journal of Veterinary Dermatology 2000; 6: 1720.
11. Fontaine, J., Beco, L., Paradis, M. Alopcie rcidivante
des flancs: tude de douze cas chez le griffon Korthals.
Point Vtrinaire 1998; 29: 4459.
12. Elder, D., Elenitsas, R., Jaworsky, C. et al. eds. Levers
Histopathology of the Skin VIII. Lippincott-Raven,
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lupus erythematosus. In: Beutner, E.H., Chorzelski, T.P.,
Kumar, V., eds. Immunopathology of the Skin, 3rd edn.
Churchill Livingstone, New York, 1987: 499518.
14. Declercq, J., Vanstapel, M.J. Chronic radiant heat dermatitis (erythema ab igne) in 2 dogs. Veterinary Dermatology 1998; 9: 26975.
15. Walder, E.J., Hargis, A.M. Chronic moderate heat dermatitis (erythema ab igne) in 5 dogs, 3 cats, and 1 silvered
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Rsum Une dysplasie folliculaire rcidivante ou persistante, associe une dermatite dinterface est rapporte
chez neuf Boxers. Les donnes relatives lge, au sexe, la saisonnalit de lalopcie et les images histopathologiques de la dysplasie folliculaire de ces neuf Boxers sont comparables celles rapportes dans les rapports prcdents. La dermatite dinterface est caractrise par des lesions multifocales, annulaires, croteuses,
confines aux zones de dysplasie folliculaire. Les lsions inflammatoires ne sont jamais prurigineuses ou douloureuses, et ltat general est bon. Sur un plan histopathologique, les lsions inflammatoires sont caractrises
par une dermatite dinterface. Des tudes immunohistochimiques nont pas permis de mettre en vidence des
immunoglobulines ou du complment au niveau de la membrane basale, ou dans les parois des vaisseaux sanguins. Chez les chiens prsentant une maladie rcidivante ou permanente, les images de dysplasie folliculaire et
de dermatite dinterface ont galement prsent des episodes de gurison spontane puis de rcidive ou ont persist. Un chien a t trait aves succs par lassociation de ttracyclines et de nicotinamide pour la dermatite
dinterface et de mlatonine pour la dysplasie folliculaire. Bien que ltiopathognie de cette maladie nouvelle et
que les relations entre les deux types de modalits ractionnelles microscopiques restent peu claires, la photopriode et une predisposition gntique pourraient jouer un role.
2003 European Society of Veterinary Dermatology, Veterinary Dermatology, 14, 159166
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M. A. Rachid et al.
Resumen Se describe una displasia folicular recurrente o persistente y una dermatitis de interfase en nueve Boxers. Los datos sobre edad, sexo, estacionalidad de la alopecia y caractersticas histopatolgicas de la displasia
folicular en estos nueve Boxers son similares a otros casos descritos en trabajos anteriores. La dermatitis de interfase fue caracterizada por lesiones multifocales anulares y costrosas confinadas a las reas de displasia folicular.
Las lesiones inflamatorias no eran ni prurticas ni dolorosas y los perros afectados se encontraban en buen estado
de salud. Histopatologicamente las lesiones clnicamente inflamatorias se caracterizaron como una dermatitis
de interfase. Los estudios inmuno-histoqumicos no pudieron demostrar inmunoglobulinas o complemento en
la zona de la membrana basal o en las paredes de los vasos sanguneos. En perros con enfermedad recurrente o
persistente, la displasia folicular y la dermatitis de interfase siguieron cursos idnticos, concurrentes en la remisin
espontnea y la repeticin, o la persistencia, respectivamente. Un perro con enfermedad persistente fue tratado
con xito: tetraciclinas y niacinamida para la dermatitis de interfase y melatonina para la displasia folicular.
Aunque la etiopatogenia de esta nueva condicin descrita y la relacin entre los dos patrones histolgicos no se
conocen, factores como el fotoperodo y la predisposicin gentica parecen desempear un papel.
Zusammenfassung Rezidivierende oder persistierende follikulre Dysplasie und Dermatitis der Grenzzone
wird bei neun Boxern beschrieben. Alter, Geschlecht, Saison und histopathologische Befunde der follikulren
Dysplasie bei diesen neun Boxern ist mit denen frherer Berichte vergleichbar. Die Dermatitis der dermalenepidermalen Grenzzone war durch multifokale, annulre, krustige und auf die Bereiche der follikulren Dysplasie
begrenzte Lsionen beschrnkt. Die entzndeten Bereiche waren weder juckend noch schmerzhaft und betroffene Hunde waren ansonsten gesund. Histopathologisch waren die klinisch entzndeten Lsionen als Dermatitis
der Grenzzone charakterisiert. Immunhistochemische Studien zeigten weder Immunglobuline noch Komplement in der Basalmembranzone oder den Blutgefsswnden. Bei Hunden mit rezidivierender oder persistierender
Erkrankung zeigten die follikulre Dysplasie und Dermatitis der Grenzzone einen identischen Verlauf von Spontanremission und Rezidiv oder Persistenz. Ein Hund mit persistierender Dermatitis wurde erfolgreich behandelt:
Tetrazyklin und Niacinamid fr die Dermatitis der Grenzzone und Melatonin fr die follikulre Dysplasie.
Obwohl die tiopathogenese dieses neu beschriebenen Syndroms und die Beziehung zwischen den beiden
histologischen Reaktionsschemata nicht bekannt sind, scheinen Photoperiode und genetische Prdisposition
eine Rolle zu spielen.