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Israel Journal of Veterinary Medicine  Vol. 70 (2)  June 2015 45 Trapped Neutrophil Syndrome in a Border Collie
Confrmed Trapped Neutrophil Syndrome in a Border Collie Puppy
in Israel
Gans, Z.
Knowledge Farm Emergency and Specialty Center, Beit Berl, Israel.
*
Corresponding Author: Dr. Zeev Gans, Knowledge Farm Emergency and Specialty Center, Beit Berl, Israel. Telephone number: 054-3114597, Email:
Zeev@emergency-veterinary.co.il
ABSTRACT
Te case report describes a Border collie puppy diagnosed with trapped neutrophil syndrome (TNS), an
autosomal recessive inherited neutropenia. Te report describes the clinical presentation, the course of
the disease and diagnosis. Chronologically it appeared that that vaccination may have been a potential
initiating factor in instigating the TNS in the puppy. Te puppy also developed clinical signs of hypertrophic
osteodystrophy (HOD). It was not possible to determine whether either vaccination and/or the development
of HOD were coincidental. To the best knowledge of the author this is the frst genetically confrmed case
of TNS described in Israel and the frst case documented outside the U.K or Australia. It is recommended
that TNS should be weighed as a possibility in any Border collie puppy which presents with symptoms of a
vague illness and confrmed neutropenia.
Keywords: Persistent Neutropenia; Hypertrophic Osteodystrophy; Trapped Neutrophils
Syndrome; Bone Marrow Hypercellularity; Border Collie.
INTRODUCTION
Trapped neutrophil syndrome (TNS) is an autosomal reces-
sive inherited neutropenia known in Border Collies since the
1990’s (1). Te clinicopathologic presentation of the disease is
an immuno-defciency characterized by peripheral neutrope-
nia and retention of neutrophils in the bone marrow. Clinical
signs often appear by 16 weeks of age. Persistent or recurrent
infections usually result in death or euthanasia at less than
one year of age (1, 2, 3). Te causative mutation has been
identifed in the canine VPS13B gene and a DNA-based
diagnosis is available (4). Long term prognosis is usually poor
although 2 cases of successful long term management have
been described (3).
CASE DESCRIPTION
A two month old Male Border Collie born in a litter of fve
to working farm dogs without any known medical conditions.
Te breeder reported that the dog was in good health since
its delivery but was about 25% smaller than its littermates.
Te dog received its frst puppy DA2LPP vaccination
and was adopted out to a family 5 days later. Te new own-
ers changed the diet and presented the dog to the referring
veterinarian two days after adoption, reporting occasional
vomiting and watery yellowish diarrhea, weakness, partial
anorexia and reluctance to walk. On examination the dog
was quiet yet responsive, vitals normal but it was unwilling
to stand. Te dog ate Hill’s A/D canned diet (Hill’s Science
Diet, USA) at the clinic and was discharged with metroni-
dazole 15mg/kg PO BID for 7 days.
Two days later, on re-examination the dog was am-
bulatory, more alert with fewer sings of diarrhea. Te dog
continued to improve and presented for its second DALPP
vaccination. One day later the dog was brought into the clinic
in a depressed, weak and anorexic Te dog was given an injec-
tion of dexamethasone SP (dose unknown) and I/D canned
Case Reports
Israel Journal of Veterinary Medicine  Vol. 70 (2)  June 2015 Gans, Z. 46
food (Hill’s Science Diet, USA). Two days later the owners
reported mild improvement followed by a deterioration of
its overall condition.
At the next visit, the dog was weak and was hospitalized
overnight with Lactate Ringer’s Solution IV, doxycycline sus-
pension 10mg/kg PO SID and amoxi-clavulonic acid 12mg/
kg PO BID. Te next day the dog was discharged eating and
drinking, with instructions to feed high quality puppy food
and physical therapy exercises. Eight days after discharge
the owners reported continued improvement followed by
an acute deterioration. On presentation the following day
the dog was weak, unwilling to stand, anorexic, with painful
forelimbs on palpation.
At that point, 25 days after adopting the dog it was re-
turned back to the breeder. A complete blood count (CBC)
and chemistry profle revealed the following abnormal fnd-
ings: Leukopenia, neutropenia, anemia (Hematocrit = 29%),
thrombocytopenia, and low blood urea nitrogen and albumin
concentrations.
Trombocytopenia and neutropenia were not confrmed
on a blood smear evaluation. Te dog was hospitalized with
LRS IV, amoxi-clavulonic acid 12mg/kg PO BID, enrofoxa-
cin 5mg/kg SQ BID, Vitamin B12 500mg IM, and iron inj
(dose/brand unknown). After 2 days of supportive therapy
without signifcant clinical change the dog was referred to
“Knowledge Farm Emergency and Specialty Center” .
Upon arrival to the Knowledge Farm hospital the dog
was quiet but responsive. Auscultation was normal for heart
and lungs, abdominal palpation was normal and the body
temperature was 38.3
o
C. Te dog was reluctant to stand or
walk but was able to stand assisted. Neurological examination
revealed normal refexes and normal cranial nerves without
conscious proprioception defcits in all 4 limbs. Both elbows
were swollen and painful and marked pain was also noted
on palpation of both forelimbs proximal to the carpii. A
complete blood count was repeated (Procyte Dx, IDEXX
Diagnostics, Westbrook, Maine, USA): Te dog was anemic
(Hematocrit=23.5%) with a severe leucopenia and neutrope-
nia and a mild thrombocytopenia. Te results were confrmed
on blood smear evaluation.
Te dog was treated with Lactated Ringer’s Solution
(Hartman’s Solution, Teva Medical Ltd., Ashdod, Israel) IV
overnight. Te appetite returned but the puppy was still pain-
ful and reluctant to stand the next day. Radiographs of the
fore- and hindlimbs demonstrated mild soft tissue swelling
around both elbows and radiolucent lines in the metaphyseal
areas of the distal radius, ulna, tibia and fbula of all 4 limbs,
consistent with hypertrophic osteodystrophy (HOD).
Te neutropenia along with the swollen elbows raised a
concern for septic arthritis. Te owner declined additional
diagnostics and Metronidazole (Flagyl, Sanof-Avetnis,
Israel) was added to the dog’s treatment as well as Carprofen
(Rimadyl, Zoetis) 2.2mg/kg PO SID-BID as was required
by pain assessment.
Due to the likelihood that the dog could not become a
working dog, it was donated to the hospital and continued to
receive supportive care both at the hospital and at one of the
veterinarian’s home for the next month and a half. During
that time, the dog exhibited cyclic clinical signs which in-
cluded fever (up to 41.6
o
C), anorexia and reluctance to walk
– all intermittently, with apparently “normal days in between”.
During hospitalization CBC’s and blood smear evaluations
were performed on multiple occasions and marked neutro-
penia was always present. Te lowest neutrophil count was
found to be 0.73x10
3
/µL and the highest 3.99x10
3
/µL.
Serologic analysis for Neospora caninum and Toxoplasm
gondii were sent to the laboratory of the Kimron
Veterinary Institute, Beit Dagan and was found to be
negative. Cobalamine levels were checked
(A.M.L Veterinary
Department, Herzlia, Israel) and found to be elevated 989ρg/
mL (Reference Interval 300-800 ρg/mL). A blood sample
was sent for genetic testing (VHL Genetics, Wageningen,
Te Netherlands) for Trapped Neutrophil Syndrome (TNS)
evaluation. Repeated radiographs exhibited resolving HOD
of the fore- and hind limbs.
Approximately 1.5 months after its arrival at the referral
hospital, the dog became once again febrile and anorexic and
developed bloody diarrhea. Its blood glucose was 57 mg/
dL and abdominal ultrasound scan revealed severe enteritis,
mesenteric lymphadenopathy and mild ascites. Blood smear
demonstrated marked neutropenia with neutrophils ap-
pearing toxic. Te assessment was of sepsis and the dog was
humanely euthanized.
Immediately after the euthanasia a femur was removed
and sent for histological evaluation (PathoVet Ltd., Rehovot,
Israel). Te marrow examination revealed hypercellularity with
a high myeloid:erythroid ratio and predominance of hyperseg-
mented neutrophils. Megakaryocyte numbers were estimated
to be in the normal range showing orderly maturation. Te
myeloid granulocytic reserve was observed to be high.
Case Reports
Israel Journal of Veterinary Medicine  Vol. 70 (2)  June 2015 47 Trapped Neutrophil Syndrome in a Border Collie
Te results of the genetic testing confrmed the diagnosis
of TNS. Tis dog was homozygously afected for the muta-
tion, indicating that both parents were carriers. Te breeder of
this dog declined further genetic testing of the dog’s parents
or siblings.
DISCUSSION
Te main diferentials for this dog’s persistent neutropenia in-
cluded TNS, familial cobalamine defciency (described in this
breed) (5) and cyclic neutropenia which has been described
in Gray collies (6). Vitamin B12 levels were normal and the
dog’s neutrophil counts did not improve with cobalamine
treatments. Repeated CBC’s and blood smear evaluations
did not reveal normal neutrophil counts at any point of time,
making both of these diagnoses unlikely. Parvoviral enteritis
was not considered a likely diagnosis due to the chronicity of
the neutropenia and lack of signifcant gastrointestinal signs
for the most part of the course of the disease.
Te swollen joints in addition to the marked neutrope-
nia raised a concern for septic arthritis. Arthrocentesis was
not performed primarily due to fnancial consideration but
was also a concern for iatrogenic introduction of infectious
agents into the joints due to the neutropenia. Radiographs of
multiple joints were more consistent with HOD than septic
arthritis. Broad spectrum antibiotics were given in case a
septic agent was after all present.
HOD is a syndrome seen mostly in large breed growing
puppies 3-4 months of age. Te etiology of HOD is not clear,
but an auto-immune etiology has been suggested (7, 8). HOD
is also a major feature in “Weimaraner Immunodefciency
Syndrome” in which neutrophil dysfunction or failure to
produce sufcient IgA/IgG antibody levels have been sug-
gested as possible causes (9, 10). It was interesting to fnd two
apparently disconnected conditions in this dog, one involving
a neutrophil disorder and the other HOD, which may suggest
some connection between the two syndromes.
Another interesting observation is that vaccination has
been implicated as a potential instigating cause of HOD
and may also have been a factor in preceding the clinical
symptoms in this dog with TNS. It is difcult to determine
whether this is a temporal coincidence or a true cause and
efect.
Tis dog initially responded to supportive therapy but
eventually developed severe gastroenteritis with hypoglyce-
mia. Furthermore the toxic changes in the neutrophils were
suggestive of sepsis resulting in the decision for euthanasia
at only 5 months of age. Immunomodulatory therapies as
well as corticosteroids were not used to manage this dog’s
condition.
Genetic testing defnitively confrmed a diagnosis of TNS
and histological evaluation of the bone marrow revealed a
hypercellular bone marrow, a high myeloid:erythroid ratio,
and a high myeloid granulocyte reserve.
Te clinical presentation and clinical course of disease
in this dog is consistent with previously published reports,
consisting of intermittent pyrexia, lethargy, HOD like bone
lesions, joint pain and gastrointestinal signs (1, 2, 3).
It is possible that in cases when owners do not want to
wait for genetic testing results in a sick puppy (which may
take several weeks), a bone marrow aspirate may be a rapid
method to diferentiate between TNS and other similar
syndromes based on the presence of a hypercellular marrow.
Interviews with several Border collie breeders in Israel
revealed “Parvoviral” related death cases in well vaccinated
puppies, suggesting the possibility that some of this pup-
pies were actually TNS cases rather than truly parvoviral
infections.
TNS is a relatively newly recognized disease entity,
which has been identifed in Britain and Australia since
the 1990’s but relatively little has been published about
it and its existence is not widely known in the practicing
veterinary community. In addition, to the best of my knowl-
edge, no confrmed cases outside the U.K or Australia have
been documented and certainly not in Israel. It is recom-
mended that TNS should be weighed as a possibility in any
Border collie puppy in Israel (and likely worldwide) which
presents with symptoms of a vague illness and confrmed
neutropenia.
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Case Reports