Demodectic Mange Associated With Lymphoma in a Ferret

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Demodectic Mange Associated With Lymphoma in a Ferret
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Demodectic Mange Associated With
Lymphoma in a Ferret
Hugues Beaufrere, Dr.Med.Vet.,
Michal Neta, DVM,
Dale A. Smith, DVM, DVSc,
and W. Michael Taylor, DVM

              Abstract
              Clinical demodicosis is rare in the ferret, and in other species this condition is
              commonly associated with concurrent immunosuppression. A 4-year-old ferret was
              examined for alopecia of the face and tail. Skin scrapings of the face and otic
              cerumen preparations revealed the presence of a large number of Demodex species.
              The ferret was also diagnosed with adrenal cortical disease based on clinical signs
              and elevated blood estradiol. Dermatologic lesions improved with oral ivermectin
              treatment, but the ferret re-presented for lethargy, weight loss, and anorexia 3
              weeks later. Ultrasound-guided fine-needle aspirates from an enlarged mesenteric
              lymph node and the spleen revealed cytologic abnormalities consistent with high-
              grade lymphoma. This case description is the first, to our knowledge, of sponta-
              neous clinical demodicosis in a ferret. Copyright 2009 Elsevier Inc. All rights
              reserved.

              Key words: demodicosis; Demodex species; ferret; immunosuppression; lymphoma

A
        924-gram, 4-year-old neutered male ferret was         logic examination revealed periorbital, peribuccal,
        presented to the Veterinary Teaching Hospi-           and tail hair loss (Fig 1). Affected facial skin was also
        tal, Ontario Veterinary College, University of        erythematous and thickened with small follicular
Guelph for assessment of hair loss and pruritus               papules. Examination of the ears showed increased
around the eyes, mouth, and tail. The diet consisted
of pelletized ferret food (Totally Ferret; Perfor-
mance Foods Inc., Broomfield, CO USA). The
owner reported that the hair loss and pruritus had               From the Department of Veterinary Clinical Sciences, Louisiana
started 9 months previously and was initially                 State University–School of Veterinary Medicine, Baton Rouge,
treated by another veterinarian with imidacloprid-            LA USA, Department of Pathobiology, Ontario Veterinary College,
moxidectin spot-on (Advantage Multi; Bayer Health             University of Guelph, Guelph, Ontario, Canada, and the Avian
Care, Toronto, Canada) once monthly for 6 months.             and Exotic Service, Veterinary Teaching Hospital, Ontario Veter-
                                                              inary College, University of Guelph, Guelph, Ontario, Canada.
The lesions resolved after the 6-month treatment but
                                                                 Address correspondence to: Hugues Beaufrere, Dr.Med.Vet.,
recurred 1 month before presentation. Another fer-
                                                              Department of Veterinary Clinical Sciences, Louisiana State Uni-
ret in the household was unaffected.                          versity–School of Veterinary Medicine, Skip Bertman Dr, Baton
   On presentation, the ferret was bright and alert.          Rouge, LA 70803. E-mail: hbeaufrere@vetmed.lsu.edu.
Abnormalities noticed during the external physical               © 2009 Elsevier Inc. All rights reserved.
examination included a mildly painful cranial abdo-              1557-5063/09/1801-$30.00
men and a moderately enlarged spleen. Dermato-                   doi:10.1053/j.jepm.2008.10.007

Journal of Exotic Pet Medicine, Vol 18, No 1 ( January), 2009: pp 57– 61                                                    57
Demodectic Mange Associated With Lymphoma in a Ferret
58                                                                                                                     Beaufrere et al

                                                                       underlying disease might have been the primary
                                                                       cause of the patient’s immunosuppressive state.
                                                                           Three weeks after the initial presentation, the
                                                                       ferret was re-presented for lethargy, anorexia, and
                                                                       weakness. The facial dermatologic lesions had mildly
                                                                       improved with hair regrowth, decreased erythema,
                                                                       and reduced amount of cerumen (Fig 2); however,
                                                                       skin scrapings were not repeated. Within the cranial
                                                                       abdomen, a small, apparently painful mass was noted
                                                                       on palpation. The ferret had lost 18% of its body
                                                                       weight since initial presentation and now weighed
                                                                       755 g. Core body temperature was 36.5°C (reference
                                                                       range, 37.8-40°C) and blood glucose was 4 mmol/L
Figure 1. Peribuccal and periocular alopecia, erythema, and skin       (reference range, 3.4-7.4 mmol/L).2 Electrolytes and
thickening in a ferret. Demodex species were found in skin scrapings   blood gas analysis revealed a moderate respiratory
from these areas.                                                      acidosis with pH: 7.13, HCO3-: 21.3 mmol/L, and
                                                                       pCO2: 63.6 mm Hg (reference ranges in the cat, pH:
                                                                       7.277-7.409, HCO3-: 18-23.2 mmol/L, pCO2: 32.7-
amounts of brown cerumen and erythema of the                           44.7 mm Hg).3 Indirect arterial systolic blood pres-
auricular ducts.                                                       sure was normal. Supportive care was initiated with
   The ferret was anesthetized with isoflurane, and a                  intravenous fluid administration (Lactated Ringer’s
blood sample was collected from the cranial vena                       solution ⫹ KCl 20 meq/L ⫹ dextrose 5%) and tri-
cava, 4 skin scrapings were taken from the face, and                   methoprim/sulfamethoxazole (15 mg/kg, every
several cerumen samples were collected from the                        12 hours, intravenously, Tribrissen 48% injection;
ears. Microscopic examination of skin scrapings and                    Schering-Plough, Pointe Claire, Canada). An ab-
the cerumen preparations revealed a large number                       dominal ultrasound examination was performed
of adults and larvae of Demodex species that were                      and revealed an enlarged mesenteric lymph node
morphologically similar to the large-bodied D. canis                   measuring 4.2 ⫻ 2.5 ⫻ 4.2 cm with a complex echo-
in dogs. Otodectes cynotis was not present in the ceru-                genicity and predominantly hypoechoic tissue. The
men preparations. Cytology of the skin surface was                     spleen contained 6 to 8 hypoechoic nodules within
unremarkable, thus bacterial culture was not per-                      its parenchyma. Adrenal gland sizes were within nor-
formed. The complete blood count and bioche-                           mal limits, with 0.35 ⫻ 0.29 ⫻ 0.79 cm for the left
mistry profile were unremarkable. A ferret adrenal                     and 0.38 ⫻ 0.26 ⫻ 0.74 cm for the right (reference
hormone panel submitted to the University of Ten-                      range, left 4-8.1 ⫻ 1.8-3.9 mm; right 4.9-10.6 ⫻ 1.3-
nessee Endocrinology Laboratory revealed an in-                        3.7 mm).4 Fine-needle aspirates were collected from
creased estradiol level at 195.2 pmol/L (reference
                                                                       the lymph node and the splenic nodules.
range provided by the University of Tennessee: 20-
                                                                           The lymph node aspirates (Fig 3) consisted al-
180 pmol/L) with normal 17␤-hydroxyprogesterone
                                                                       most exclusively of highly monomorphic lympho-
and androstenedione blood levels. Abdominal ultra-
sound examination was declined at that time.
   After the physical examination and diagnostic test
results, a tentative diagnosis was facial demodectic
mange and adrenal cortical disease. The ferret was
treated with an injection of leuprolide acetate (100
␮g, intramuscularly, Lupron Depot; TAP Pharma-
ceuticals, Lake Forest, IL USA). He was also sent
home with oral ivermectin (50 ␮g/kg every 24 hours,
orally, Ivomec; Merial Limited, Duluth, GA USA).
The dosage was progressively increased over the first
2 weeks to 300 ␮g/kg, and the overall treatment was
planned to last until 1 month after negative skin
scrapings. Progressive dosage increase was elected as
                                                                       Figure 2. Mild improvement of dermatologic lesions caused by
recommended in the dog.1 The owner was encour-                         Demodex species 3 weeks after starting oral ivermectin treatment.
aged to permit an abdominal ultrasound examina-                        The skin was less erythematous and thickened, and the auricular
tion as soon as possible to determine whether an                       ducts were less inflamed.
Demodectic Mange Associated With Lymphoma in a Ferret
Demodicosis in a Ferret                                                                                                           59

                                                                    alopecia and pruritus that were diagnosed with de-
                                                                    modicosis based on skin scrapings and biopsies.
                                                                       Demodex species are thought to live as commensals
                                                                    in the hair follicles and sebaceous glands of most
                                                                    mammals and may proliferate with an underlying
                                                                    immunological deficiency.9 A retrospective his-
                                                                    topathologic study on normal ferret skin found 9 of
                                                                    25 ferrets, aged 4 to 32 months, with commensal
                                                                    Demodex species present within the hair follicles and
                                                                    sebaceous glands in the perianal, vulvar, preputial,
                                                                    facial, and caudal abdominal regions.10 Adult onset
                                                                    of demodectic mange in dogs and cats is generally
                                                                    triggered by conditions altering the immune system,
                                                                    most commonly Cushing’s disease, hypothyroidism,
                                                                    diabetes mellitus, immunosuppressive drug therapy,
Figure 3. Cytological appearance of a fine-needle aspirate of the   feline immunodeficiency virus infection, feline leu-
mesenteric lymph node from a ferret with lymphoma and concurrent    kemia virus infection, or neoplasia.1,9 In the previous
demodicosis. There were large monomorphic lymphocytes, with
frequent mitotic activity (arrows). Wright’s stain, bar ⫽ 10 ␮m.    case report by Noli and coworkers, demodicosis was
                                                                    induced by the use of a glucocorticoid-based oint-
                                                                    ment containing triamcinolone (Tresaderm; Merial
cytes. These were large cells (approximately 30 ␮m                  Limited, Iselin, NJ USA) for 3 months for the treat-
in diameter) with increased nuclear-cytoplasmic ra-                 ment of recurrent ear mite infestations.8
tios. Cytoplasm was grainy and stained deeply baso-                    The dermatologic lesions in this ferret responded
philic. There was sparse cytoplasmic vacuolation and                twice to acaricidal therapy. Postmortem examination
small, indistinct Golgi zones. Nuclei were large, with              and histopathology of the skin would have been very
a finely reticulated chromatin pattern and occa-                    informative but were declined by the owner. Skin
sional obscure nucleoli. There was minimal anisocy-                 scrapings were not repeated at the 3-week recheck
tosis and anisokaryosis, but mitotic activity was high              because of the early stage of the therapy. The two
(2-4 mitotic figures per high power field). The aspi-               ferrets described by Noli and coworkers showed der-
rate from the spleen (Fig 4) was extremely cellular                 matologic lesions consisting of alopecia and sebor-
and revealed extensive extramedulllary hematopoie-                  rhoea localized behind the ears, in the inguinal ar-
sis which is commonly seen in ferrets. However,                     eas, and on the ventral aspect of the tail with an
among the hematopoietic precursors were low num-                    increased cerumen production in the ears. Skin
bers of large lymphocytes, morphologically similar to
those noted in the mesenteric lymph node and with
high mitotic activity. These cells were scattered in a
patchy, uneven distribution and, although overall
they were not a prominent population, they were
clearly abnormal and predominated in certain areas
of the slide. Findings were interpreted as a high-
grade lymphoma in the mesenteric lymph node and
the spleen.
   The ferret’s clinical condition did not improve
over 24 hours, and the owner requested euthanasia.
Postmortem examination was declined. The final
diagnosis was demodicosis secondary to a general-
ized lymphoma with concurrent adrenal cortical dis-
ease.

Discussion
                                                                    Figure 4. Cytological appearance of a fine-needle aspirate of the
                                                                    spleen from a ferret with lymphoma and concurrent demodicosis.
Clinical demodicosis is considered an uncommon                      Large lymphocytes are present among hematopoietic precursors.
dermatosis of ferrets and has rarely been reported.5-7              Megakaryocytes (MK) and a mitotic figure (arrow) were also noted.
Noli and coworkers8 described two ferrets with local                Wright’s stain, bar ⫽ 10 ␮m.
Demodectic Mange Associated With Lymphoma in a Ferret
60                                                                                                       Beaufrere et al

scrapings, smears of exudates from the ears, and skin       in association with lymphoproliferative disorders has
biopsies revealed the presence of adult and larvae of       been described in dogs, cats,9,14 and humans.15-17
a short-bodied Demodex species. However, localiza-          Immune depression or suppression predisposes to a
tion of skin scrapings and biopsies were not docu-          variety of skin diseases, including demodicosis, in
mented. They were successfully treated with amitraz         small animals.18 Deficiencies in cell-mediated im-
dips without side effects, 0.0125% at 7-day intervals       mune response play an important role in the patho-
for 3 treatments followed by 0.0375% at 5-day inter-        genesis of demodicosis in humans and dogs.15 Effects
vals for 3 final treatments. The ferrets had no evi-        of lymphoma on the immune system have been
dence of mites 1 month after the end of the treat-          poorly investigated in ferrets. Although there are
ment.8 In our case, Demodex species were similarly          numerous reports of lymphoid neoplasia of ferrets
found in the skin scrapings and ear exudate but were        in the literature, none describe concurrent demodi-
different in morphology and more comparable to              cosis.19
the long-bodied dog D. canis and the Demodex species           This report is the first, to our knowledge, to
described in normal ferret skin by Martin and co-           present the spontaneous occurrence of demodectic
workers10 On skin biopsies presented by Noli and            mange in a ferret. We suggest that cases of con-
coworkers, the mites were superficial and not seen in       firmed demodicosis be screened carefully for the
the sebaceous glands and deeper portions of the hair        presence of an underlying disease process that re-
follicles, whereas the commensal Demodex species re-        sults in an immunosuppressive state.
ported by Martin and coworkers were present in the
sebaceous glands. This suggests two different species
of Demodex, the one recovered from our ferret being
more consistent with the report from Martin and
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