Alopecia universalis in a dog with testicular neoplasia

Catherine A. Outerbridge*, Stephen D. White* and Verena K. Affolter†

*Departments of Medicine and Epidemiology and †Pathology, Microbiology & Immunology, School of Veterinary Medicine, University of CaliforniaDavis, 1 Garrod Drive, Davis, CA 95616, USA

Correspondence: Catherine A. Outerbridge, Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California

Davis, 1 Garrod Drive, Davis, CA 95616, USA. E-mail: caouterbridge@vmth.ucdavis.edu

Objective – To describe a case of testicular neoplasia and alopecia universalis in a dog, and successful treatment

of the latter with ciclosporin.

Animal – Twelve-year-old intact male wirehaired fox terrier.

Methods – Castration, skin biopsy for histopathology, lymphocyte immunophenotyping and clonality analysis of

the canine T-cell receptor gamma locus (TCRc) rearrangement.

Results – The dog presented with symmetrical generalized alopecia. Testicular enlargement was noted which

on castration was determined to be caused by bilateral interstitial cell tumours, Sertoli cell tumours and a unilat-

eral seminoma. During the four months after castration the alopecia became more severe and widespread.

Histopathology of the skin showed moderate, multifocal, mural folliculitis, peribulbar mucinosis and lymphocytic

bulbitis, and targeting of anagen hair follicles. Immunophenotyping of the infiltrate showed a population of well-

differentiated, small CD3-positive T lymphocytes, some expressing CD4 and others CD8. Molecular analysis

revealed a polyclonal lymphocytic infiltrate, substantiating the diagnosis of alopecia areata rather than lymphoma.

Treatment with ciclosporin (4.6 mg/kg) and ketoconazole (4.6 mg/kg) resulted in complete hair regrowth.

Conclusion and clinical importance – Ciclosporin treatment, in combination with ketoconazole, can be effec-

tive for treatment of alopecia universalis in the dog. Alopecia universalis may present with clinically noninflamma-

tory, symmetrical, generalized alopecia, mimicking an endocrine alopecia, and skin biopsies are needed to

confirm the diagnosis.

Introduction

Alopecia areata is a rare cause of alopecia in the dog.1–4

Most reports describe patchy alopecia, often involving

the face, which may progress to the pinnae and legs.2 In

humans, the most severe form of alopecia areata is ter-

med alopecia universalis and is defined as loss of hair

over the entire body.5 Histological examination of skin

biopsy specimens in dogs with alopecia areata reveals

the presence of peri- and intrabulbar mononuclear cell

infiltrates targeting anagen hair follicles.2,6,7 Alopecia

areata is theorized to be a T-cell mediated autoimmune

disorder.5 In one study, 60% of dogs with alopecia areata

underwent spontaneous hair regrowth within months of

the diagnosis.6

This case report describes a dog with alopecia areata

that also had testicular neoplasia. Testicular neoplasia can

cause alopecia resulting from increased serum levels of

estrogen and/or testosterone associated with testicular

tumour(s).2,8 The alopecia associated with these hor-

mone imbalances most often involves the caudal thighs

and trunk, histopathology showing a follicular growth

cycle arrest with hairless telogen follicles predominating.7

The alopecia resolves upon surgical removal of the testic-

ular tumour.2 As spontaneous hair regrowth was not

observed following castration, the dog was treated with

ciclosporin and after two months of therapy complete

hair regrowth occurred.

Case report

A 12-year-old intact male wirehaired fox terrier presented

for evaluation of a six month history of progressive, non-

pruritic alopecia. Hair loss began on the lateral trunk and

rapidly progressed to involve almost the entire trunk, cer-

vical region, proximal limbs and dorsal muzzle. The refer-

ring veterinarian had documented a low resting serum

thyroxine value of 0.9 lg/dL (reference range 0.8–5.0 lg/dL) and prescribed oral levothyroxine (0.02 mg/kg twice

daily). After three months supplementation had failed to

improve the alopecia, 3 mg of melatonin daily for

two months was prescribed, with no improvement

noted. There was a history of possible polyuria and poly-

dipsia, thus blood samples were submitted for a com-

plete blood cell count, serum biochemistry panel and pre-

and post-ACTH stimulation cortisol levels. All results

were within normal limits.

At the time of presentation, the only medications that

the dog was receiving were melatonin and levothyroxine.

On physical examination there was marked bilateral trun-

cal alopecia also involving the proximal limbs and dorsal

muzzle (Figure 1a). The skin was mildly hyperpigmented

Accepted 27 July 2016

Sources of Funding: This study was self-funded.

Conflict of Interest: No conflicts of interest have been declared.

This case report was presented as a brief communication at the

North American Veterinary Dermatology Forum, 2008; Denver,

CO, USA.

© 2016 ESVD and ACVD, Veterinary Dermatology, 27, 513–e139. 513

Vet Dermatol 2016; 27: 513–e139 DOI: 10.1111/vde.12380

and noninflamed. The remaining hair coat was dry, com-

pacted with areas of matting. In addition to the alopecia,

there was nonpalpable linear erythema and hyperpigmen-

tation on the midline of the prepuce extending from the

preputial orifice to the scrotum. Palpation of the testes

revealed asymmetry, the right larger than the left, and a

palpable mass in the caudal pole of the right testis.

Castration was recommended with the suspicion that

the alopecia might be caused by a sex hormone imbalance

from testicular neoplasia. The dog was castrated and both

testes along with skin biopsies from the preputial linear

skin lesion were submitted for histopathology. The prepu-

tial skin was biopsied to determine what histopathology

might account for this feature, previously reported as a

cutaneous marker for testicular neoplasia, especially

tumours that produce estrogens.2 Histopathology of the

testes revealed bilateral interstitial cell tumours, bilateral

Sertoli cell tumours and a unilateral seminoma. The biopsy

of the preputial skin showed no histopathological changes.

Biopsies from the alopecic areas were not collected

because hypothyroidism and hyperadrenocorticism were

felt to have been adequately controlled/ruled out. Sex hor-

mone assays were not performed.

The dog represented four months after castration for re-

evaluation. The linear preputial erythema and pigmentation

had resolved, but the alopecia had progressed to involve

most of the limbs as well as most of the head including

vibrissae and eyelashes. (Figure 1b) The skin was still

noninflamed and the dog was not pruritic. Multiple skin

biopsies were taken from the trunk, lateral thigh and

top of the head. Histopathological evaluation revealed

moderate, multifocal, mural folliculitis with peribulbar

mucinosis (Figure 2a); this latter finding was confirmed

by staining with Alcian blue. There was also some follic-

ular atrophy and perifollicular pigmentary incontinence.

Closer visualization of the hair bulb revealed numerous

lymphocytic infiltrates around and within the hair bulb

(lymphocytic bulbitis) (Figure 2b). The histological find-

ings were typical of alopecia areata, which was further

supported clinically by the generalized alopecia. How-

ever, the dog’s age, mucinosis and the intensity of the

lymphocytic infiltrate raised concerns of an atypical his-

tological presentation of folliculocentric epitheliotropic

lymphoma. In order to exclude this possibility, further

skin biopsies were obtained for immunophenotyping

and clonality studies.

a cb

Figure 1. (a) 12-year-old intact male wirehaired fox terrier with truncal, limb and facial alopecia. (b) The same dog as in a), now castrated, with gen-

eralized alopecia sparing the top of the head. (c) The same dog as in a) & b) two months after treatment with ciclosporin and ketoconazole.

a b

Figure 2. Histology of alopecia universalis in a wirehaired fox terrier. a) The hair bulbs are surrounded by fibrosis and mucin (⇐) and small lympho-cytes (?). Some lymphocytes are also infiltrating the hair bulb (↓). Haematoxylin and eosin (H&E); bar: 50 lm. b) There is marked circular fibrosiswith dispersed small lymphocytes (⇐) surrounding the hair bulb and numerous lymphocytes (↓) are present amongst the matrical cells. H&E, bar:50 lm.

© 2016 ESVD and ACVD, Veterinary Dermatology, 27, 513–e139.514

Outerbridge et al.

Two six mm punch skin biopsy were obtained.

Biopsies were bisected, one half fixed in formalin, the

other half immersed in OCT compound (Finetek,

Sakura USA; Torrance, CA, USA), and snap frozen as

previously described.9 Evaluation of biopsies (haema-

toxylin and eosin) and immunohistochemistry for CD3-e(CD3-12, Serotec; Oxford, UK) was performed on

formalin-fixed sections. Immunohistochemistry for CD1

(CA13.9H11), CD3 (CA17. 2A12), CD4 (CA13.1E4) and

CD8 (CA8, JD3 and CA165.4D2; Leukocyte Antigen

Biology Laboratory, UC Davis, PF Moore) was per-

formed on 5 lm cryosections. The infiltrating lymphoidpopulation was composed of CD3+ T cells, some ofwhich were CD4+ cells and others expressed CD8.Admixed there were slightly larger cells, which expressed

CD1 as well as CD4, interpreted as activated dermal

dendritic cells (Figure 3). Testing for clonality revealed

polyclonal T cell receptor-gamma (TCRc) gene rearrange-ments consistent with a reactive inflammatory process

rather than neoplasia.10,11

As no spontaneous hair regrowth was observed

and the alopecia was extensive, treatment for alopecia

areata was initiated with daily ciclosporin 4.6 mg/kg

(Atopica: Novartis Animal Health; Greensboro, NC,

USA) and concurrent ketoconazole 4.6 mg/kg (Mylan

N.V.White; Sulphur Springs, WV, USA), to permit

lower dosing of ciclosporin via the competitive P450

interaction between ciclosporin and azole antifungals.12

Hair regrowth was reported by owners to be evident

within the first four weeks after starting therapy and

full hair coat was present after two months (Fig-

ure 1c). Both medications were decreased to alternate

day dosing with no recurrence of alopecia. The dog

lived for another two years on this regimen with full

hair coat before dying of unknown causes.

Discussion

Alopecia areata is presumed to be a T-cell mediated

autoimmune process.13 Although the disease has

been reported to undergo spontaneous remission in

60% of dogs, it is difficult to know precisely how

long the alopecia areata had affected the dog in this

report, as the testicular neoplasia also could have con-

tributed to the alopecia. However, four months post-

castration the alopecia had increased in severity and

extent of body area affected. This suggests that the

regrowth of hair in this dog was due to the therapy

a b

dc

Figure 3. Inflammatory infiltrate of alopecia universalis in the reported, wirehaired fox terrier. The infiltrate is predominantly (a) CD3+ T cells (bar:50 lm) and (b) CD1+ dendritic antigen presenting cells (bar: 100 lm). The T cell population is mixed, including (c) CD4+ T cells (?) and activatedCD4 dermal dendritic cells (⇐) (bar: 50 lm) and (d) CD8+ T cells (bar: 100 lm). Immunohistochemistry on formalin-fixed tissue (a) and snap frozentissues (b–d), AEC chromagen.

© 2016 ESVD and ACVD, Veterinary Dermatology, 27, 513–e139. 515

Alopecia universalis in a dog

with ciclosporin and ketoconazole, and not sponta-

neous resolution.

Ciclosporin is theorized to be effective in the treat-

ment of alopecia areata due to its suppressive action

on T cell function, and has been used to treat the

disease in people for more than two decades.5,13 In

addition, ciclosporin has been shown to be effective

in the treatment of a rat model with alopecia

areata.14,15 Curiously, in people alopecia areata has

occurred in the face of concurrent ciclosporin treat-

ment for other diseases.16,17

The dog in this report is unusual in several ways.

First, the initial diagnosis of testicular tumours was

assessed to be the aetiology of the alopecia. The

truncal alopecia was consistent with that caused by

testicular neoplasia, although the facial alopecia would

be more expected with alopecia areata.7 When the

alopecia progressed, skin biopsies confirmed the pres-

ence of lymphocytic bulbitis and because of the near

total involvement of the body surface a diagnosis of

alopecia universalis was made. The original skin

biopsy, taken at the time of castration, was unremark-

able but was taken from the preputial skin and not

from the truncal alopecia. Hence, it is conceivable that

the alopecia areata was concomitant at the time of

diagnosis of testicular neoplasia in this dog.

Due to the extent of the lymphoid infiltrate and the fact

that cutaneous epitheliotropic lymphoma in dogs can

preferentially affect hair follicles, it was important to rule

out the presence of a clonal neoplastic T cell population

by evaluating TCRc rearrangement of the lesional cells.Interestingly, alopecia universalis has been reported in

humans in association with cutaneous epitheliotropic T

cell lymphoma.18

A previous report of ciclosporin treatment of a dog with

alopecia universalis documented only partial response.19

Likewise, another dog with alopecia areata had only par-

tial response to ciclosporin alone before being lost to fol-

low-up.20 The concurrent administration of ketoconazole

in our study dog possibly resulted in higher levels of

ciclosporin than those attained in the dogs treated with

ciclosporin alone. Ciclosporin levels in the skin were docu-

mented to be higher in research dogs receiving 2.5 mg/

kg of ciclosporin and 5 mg/kg of ketoconazole versus

dogs receiving 5 mg/kg of ciclosporin alone.12 Ciclosporin

levels were never measured in the study dog and hence

plasma or tissue levels of ciclosporin resulting from the

prescribed therapy are not known.

In conclusion, ciclosporin treatment, in combination

with ketoconazole, can be effective for treatment of

alopecia universalis in the dog. Alopecia universalis may

present with clinically noninflammatory, symmetrical,

generalized alopecia, mimicking endocrine alopecias, and

skin biopsies are needed to confirm the diagnosis.

Acknowledgement

The authors would like to thank Christopher M. Reilly for

additional histopathological evaluation.

References

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mediated dermatoses. Muller and Kirk’s Small Animal Dermatol-

ogy, 7th edition. Philadelphia, PA: Saunders, 2012, 462–463.3. Alhaidari Z. Alopecia areata in a mixed breed 9-year-old English

setter [French]. Ann Dermatol Venereol 2003; 130: 416.

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Assoc 2014; 245: 1011–1013.5. Ac�ıkg€oz G, Calıs�kan E, Tunca M et al. The effect of oral cyclos-

porine in the treatment of severe alopecia areata. Cutan Ocul

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logue of alopecia areata in humans. Br J Dermatol 2003; 149:

938–950.7. Gross TL, Ihrke PJ, Walder EJ et al. Mural diseases of the hair

follicle. Skin Diseases of the Dog and Cat, Clinical and

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lishing, 2005: 460–464.8. Mecklenburg L. Canine hyperestrogenism. In: Mecklenburg L,

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of canine T cell proliferations. Vet Immunol Immunopathol 2012;

145: 410–419.11. Keller SM, Moore PF. Rearrangement patterns of the canine

TCRgamma locus in a distinct group of T cell lymphomas. Vet

Immunol Immunopathol 2012; 145: 350–361.12. Gray L, Hillier A, Cole L et al. The effect of ketoconazole on

whole blood and skin cyclosporine concentrations in dogs. Vet

Dermatol 2013; 224: 118–126.13. Gupta AK, Ellis CN, Cooper KD et al. Oral cyclosporine for the

treatment of alopecia areata. A clinical and immunohistochemi-

cal analysis. J Am Acad Dermatol 1990; 22: 242–250.14. Oliver RF, Lowe JG. Oral cyclosporin A restores hair growth in

the DEBR rat model for alopecia areata. Clin Exp Dermatol 1995;

20: 127–131.15. Verma DD, Verma S, McElwee KJ et al. Treatment of alopecia

areata in the DEBR model using Cyclosporin A lipid vesicles. Eur

J Dermatol 2004; 14: 332–338.16. Phillips MA, Graves JE, Nunley JR. Alopecia areata presenting in

2 kidney-pancreas transplant recipients taking cyclosporine. J

Am Acad Dermatol 2005; 5(Suppl 1): S252–S255.17. Cerottini JP, Panizzon RG, de Viragh PA. Multifocal alopecia

areata during systemic cyclosporine A therapy. Dermatology

1999; 198: 415–417.18. Miteva M, El Shabrawi-Caelen L, Fink-Puches R et al. Alopecia

universalis associated with cutaneous T cell lymphoma. Derma-

tology 2014; 229: 65–69.19. Ginel PJ, Blanco B, P�erez-Aranda M et al. Alopecia areata univer-

salis in a dog. Vet Dermatol 2015; 26: 379–383.20. Noli C, Toma S. Three cases of immune-mediated adnexal skin

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R�esum�e

Objectif – D�ecrire un ca s de tumeur testiculaire et d’alopecia universalis chez un chien ainsi que le traite-

ment efficace de cette derni�ere avec la ciclosporine.

Sujet – Un fox terrier �a poil dur, mâle entier de douze ans.

M�ethodes – Castration, biopsie cutan�ee pour histopathologie, immunoph�enotypage lymphocytaire et ana-

lyse de clonalit�e pour le r�earrangement du locus gamma de TCRc (canine T-cell receptor).

© 2016 ESVD and ACVD, Veterinary Dermatology, 27, 513–e139.516

Outerbridge et al.

R�esultats – Le chien pr�esentait une alop�ecie sym�etrique bilat�erale. Une augmentation du volume testicu-

laire s’est r�ev�el�ee être, apr�es castration, li�ee �a une tumeur bilat�erale des cellules interstitielles, une tumeur

de Sertoli et un seminome unilat�eral. Au cours des 4 mois apr�es la castration l’alop�ecie s’est aggrav�ee et�etendue. L’histopathologie cutan�ee a montr�e une folliculite murale multifocale, mod�er�ee, une mucinose

p�eribulbaire et une bulbite lymphocytaire, ciblant les follicules pileux anag�enes. L’immunoph�enotypage de

l’infiltrat a montr�e une population de petits lymphocytes T CD3-positifs, bien diff�erenti�es, certains expri-

mant CD4 et d’autres CD8. L’analyse mol�eculaire a r�ev�el�e un infiltrat lymphocytaire polyclonal, favorisant

le diagnostic d’alopecia aerata plutôt que celui de lymphome. Le traitement avec de la ciclosporine

(4.6 mg/kg) et du k�etoconazole (4.6 mg/kg) a r�esult�e en une compl�ete repousse pilaire.

Conclusion et importance clinique – Le traitement �a la ciclosporine, en association avec du k�etocona-

zole, peut être efficace pour le traitement de l’alopecia universalis chez le chien. L’alopecia universalis peut

se pr�esenter par une alop�ecie g�en�eralis�ee, sym�etrique, non inflammatoire mimant une alop�ecie endo-

crienne et des biopsies cutan�ees sont n�ecessaires pour confirmer le diagnostic.

Resumen

Objetivo – Describir un caso de neoplasia testicular y alopecia universalis en un perro, y el tratamiento exi-

toso de esta �ultima con ciclosporina.

Animal – un perro macho entero Fox Terrier de doce a~nos de edad intacta de pelo duro.

M�etodos – castraci�on, biopsia de piel para histopatolog�ıa, inmunofenotipado de linfocitos y an�alisis de la

clonalidad de reordenamiento del locus receptor de c�elulas T gamma canino (TCRc).

Resultados – El perro se present�o con la alopecia generalizada sim�etrica. Se observ�o aumento del volu-

men testicular se observ�o en la tras la castraci�on se determin�o que era causado por tumores bilaterales de

c�elulas intersticiales, tumores de c�elulas de Sertoli y un seminoma unilateral. Durante los 4 meses despu�es

de la castraci�on la alopecia se hizo m�as grave y generalizada. La histopatolog�ıa de la piel mostr�o moderada

foliculitis mural multifocal, mucinosis peribulbar y bulbitis linfoc�ıtica afectando a los fol�ıculos pilosos en fase

an�agena. El inmunofenotipado del infiltrado mostr�o una poblaci�on de linfocitos peque~nos CD3-positivos y

bien diferenciados, algunos expresando CD4 y otros CD8. El an�alisis molecular revel�o un infiltrado linfocita-

rio policlonal, que justificaba el diagn�ostico de alopecia areata en lugar de linfoma. El tratamiento con ciclos-

porina (4,6 mg / kg) y ketoconazol (4,6 mg / kg) dio como resultado la regeneraci�on del completa del

cabello.

Conclusi�on e importancia cl�ınica – el tratamiento con ciclosporina en combinaci�on con ketoconazol, pue-

den ser eficaces para el tratamiento de la alopecia universal en el perro. La alopecia universal puede pre-

sentarse cl�ınicamente como alopecia no inflamatoria, sim�etrica y generalizada, semejando una alopecia

endocrina, y se necesitan biopsias de piel para confirmar el diagn�ostico.

Zusammenfassung

Ziel – Die Beschreibung eines Falls von Hodenneoplasie und einer Alopezia universalis bei einem Hund

und die erfolgreiche Behandlung letzterer mit Ciclosporin.

Tier – Ein zw€olf Jahre alter intakter rauhaariger Foxterrierr€ude.

Methoden – Kastration, Hautbiospie zur histopathologischen Untersuchung, Immunph€anotypisierung der

Lymphoyzten und eine Klonalit€atsanalyse des caninen T-Zellrezeptor Gamma Locus (TCRc) Rearrange-

ments.

Ergebnisse – Der Hunde wurde mit einer generalisierten symmetrischen Alopezie vorgestellt. Eine

Vergr€oßerung der Testikel wurde festgestellt, was nach der Kastration als bilateraler interstitieller Zelltu-

mor, Sertolizelltumor und unilaterales Seminom diagnostiziert wurde. W€ahrend der ersten 4 Monate nach

der Kastration wurde die Alopezie schlimmer und ausgedehnter. Die histopathologische Untersuchung

ergab eine moderate, multifokale, murale Follikulitis, peribulb€are Mucinose und lymphozyt€are Bulbitis,

wovon in erster Linie anagene Haarfollikel betroffen waren. Die Immunph€anotypisierung des Infiltrates

zeigte eine Population von gut differenzierten, kleinen CD3-positiven T Lymphozyten, von denen manche

CD4 und andere CD8 exprimierten. Die molekulare Analyse zeigte ein polyclonales Lymphozyteninfiltrat,

welches die Diagnose einer Alopezia areata eher unterst€utzte als die eines Lymphoms. Eine Behandlung

mit Ciclosporin (4,6 mg/kg) und Ketokonazol (4,6 mg/kg) f€uhrte zum vollst€andigen Nachwachsen der

Haare.

Schlussfolgerung und klinische Bedeutung – Eine Behandlung mit Ciclosporin in Kombination mit Keto-

konazol kann eine wirksame Behandlung einer Alopezia universalis beim Hund darstellen. Eine Alopezia

universalis kann mit einer klinisch nicht entz€undlichen, symmetrischen, generalisierten Alopezie, die eine

endokrine Alopezie imitiert, einhergehen und Hautbiospien zu Best€atigung der Diagnose n€otig machen.

要約

目的 – 精巣腫瘍と全身性脱毛症を併発し、後者についてはシクロスポリンによって治療に成功した犬の1例を紹介すること。

Alopecia universalis in a dog

© 2016 ESVD and ACVD, Veterinary Dermatology, 27, 513–e139. e138

供与動物 – 12歳齢、未去勢のワイヤー・フォックス・テリア。方法 – 去勢手術、病理組織学的検査のための皮膚生検、リンパ球の免疫表現型検査、および犬のT細胞受容体γ遺伝子再構成クローナリティ検査。結果 – 患者は対称性の全身性脱毛を呈して来院した。去勢手術時に精巣の腫大が確認され、両側性の間質細胞腫とセルトリ細胞腫瘍、および片側性の精上皮腫と診断された。去勢手術の4ヶ月後、脱毛はさらに進行拡大した。皮膚の病理組織学検査において、成長期毛を標的とした、中程度の多中心性の壁内毛包炎、毛球周囲のムチン沈着症およびリンパ球性毛球炎が認められた。免疫表現型検査において、浸潤細胞は、CD4もしくはCD8を発現する、高分化型の小型CD3陽性T細胞で構成されていた。分子学的解析では、ポリクローナルなリンパ球の浸潤が認められ、リンパ腫よりは全身性脱毛症が妥当であると診断された。シクロスポリン(4.6 mg/kg)とケトコナゾール(4.6 mg/kg)の併用治療によって、完全な再毛を認めた。結論および臨床的な重要性 – シクロスポリンとケトコナゾールの併用は、犬の全身性脱毛の治療に効果的であるかもしれない。全身性脱毛症は、臨床的には非炎症性の対称性全身性脱毛を呈し、内分泌疾患に起因した脱毛と類似するため、確定診断には皮膚生検が必要である。

摘要

目的 – 例犬睾丸肿瘤伴随全身脱毛病例,使用环孢素成功治愈脱毛。动物 – 12岁未去势刚毛猎狐梗。方法 – 摘除睾丸、取皮肤活检样本进行组织病理学检查、淋巴细胞免疫分型和犬T细胞r受体基因重排克隆分析。结果 – 该犬表现为广泛性对称性脱毛。摘除的睾丸明显增大,经检查为双侧间质细胞瘤、赛托利细胞瘤和单侧精原细胞瘤。在动物行去势术后的4个月内,脱毛更严重且更广泛。皮肤组织病理学显示为中度、多病灶性、毛囊壁炎、毛球周粘蛋白沉积和淋巴细胞性毛球炎,并且其靶向位点在生长期毛囊。浸润细胞免疫表型表现为大量分化良好的、小型CD3阳性T淋巴细胞、部分CD4表型、其他为CD8表型。分子鉴定显示为多克隆淋巴细胞性浸润,证明是斑秃而不是淋巴瘤。使用环孢素(4.6 mg/kg)和酮康唑(4.6 mg/kg)治疗后,毛发再次长出。总结和临床意义 – 环孢素合并酮康唑能够有效治疗犬全身脱毛。全身脱毛临床表现可能为非炎性的、对称的、广泛性脱毛,类似内分泌性脱毛,需要经过皮肤活组织检查进行确诊。

Resumo

Objetivo – Descrever um caso de neoplasia testicular e alopecia universalis em um c~ao, e o tratamento

bem sucedido da �ultima com ciclosporina.

Animal – Um c~ao de 12 anos de idade, macho intacto, da rac�a Fox Terrier de pelo duro.M�etodos – Castrac�~ao, bi�opsia de pele e histopatologia, imunofenotipagem de linf�ocitos e an�alise de clona-lidade do rearranjo de receptores em locus gama de c�elulas T (TCRc).

Resultados – O c~ao foi apresentado com alopecia sim�etrica generalizada. Aumento testicular foi obser-

vado. �A castrac�~ao, determinou-se que este aumento fora causado por tumores bilaterais de c�elulas intersti-ciais, sertolinoma e um seminoma unilateral, como causadores. Durante os primeiros quatro meses ap�os a

castrac�~ao, a alopecia se tornou mais grave e disseminada. Histopatologia da pele demonstrou foliculitemural moderada e multifocal, mucinose peribular e bulbite linfoc�ıtica, e alvo de destruic�~ao em fol�ıculos pilo-sos an�agenos. Imunofenotipagem do infiltrado demonstrou a populac�~ao de pequenos linf�ocitos T CD3+bem diferenciados, alguns expressando CD4 e outros CD8. An�alise molecular revelou infiltrado linfocit�ario

policlonal, reforc�ando o diagn�ostico de alopecia areata ao inv�es de linfoma. Tratamento com ciclosporina(4.6 mg/kg) e cetoconazol (4.6 mg/kg) resultou em repilac�~ao completa.Conclus~oes e importância cl�ınica – O tratamento com ciclosporina, associado com cetoconazol, pode

ser eficaz no tratamento de alopecia universalis em c~aes. Esta doenc�a apresenta-se como alopecia n~aoinflamat�oria generalizada que mimetiza alopecia end�ocrina. Bi�opsias cutâneas s~ao necess�arias para confir-

mar o diagn�ostico.

Outerbridge et al.

© 2016 ESVD and ACVD, Veterinary Dermatology, 27, 513–e139.e139