Download Cutaneous asthenia (Ehlers–Danlos syndrome

Turkish Journal of Veterinary and Animal Sciences
http://journals.tubitak.gov.tr/veterinary/
Case Report
Turk J Vet Anim Sci
(2013) 37: 245-249
© TÜBİTAK
doi:10.3906/vet-1203-64
Cutaneous asthenia (Ehlers–Danlos syndrome) in a cat
1,
2
3
Banu DOKUZEYLÜL *, Elif Demet ALTUN , Tamer Halit ÖZDOĞAN ,
4
2
1
Hasan Hakan BOZKURT , Seçkin Serdar ARUN , Mehmet Erman OR
1
Department of Internal Medicine, Faculty of Veterinary Medicine, İstanbul University, 34320 Avcılar, İstanbul, Turkey
2
Department of Pathology, Faculty of Veterinary Medicine, İstanbul University, 34320 Avcılar, İstanbul, Turkey
3
Pet Corner Veterinary Policlinics, 34394 Mecidiyeköy, İstanbul, Turkey
4
Department of Histology, Faculty of Veterinary Medicine, İstanbul University, 34320 Avcılar, İstanbul, Turkey
Received: 30.03.2012
Accepted: 09.07.2012
Published Online: 15.03.2013
Printed: 15.04.2013
Abstract: Ehlers–Danlos syndrome (EDS), or dermatosparaxis, is a rare hereditary disease of the connective tissue, which is characterized
by skin hyperextensibility and laxity. In the present article, the case of a crossbred female spayed cat, at the age of 2 years, was presented
with hyperelasticity of the skin, alopecia, and an ulcerative wound on the left hind leg. The animal’s dorsum was hyperextensible,
smooth to the touch, and could be easily torn with minor traumas. To the best of the authors’ knowledge, the present report is the first
documented feline case of cutaneous asthenia in Turkey.
Key Words: Cat, collagen disease, cutaneous asthenia, Ehlers–Danlos syndrome
1. Introduction
The Ehlers–Danlos syndrome (EDS), a group of inherited
connective tissue diseases, is recognized in animals as well
as in humans (1). Naturally occurring cases of this disease
are reported in many species: horses (2–4), cats (5–9), dogs
(10–13), calves, sheep, rabbits, and mink (2,13). However,
this disease is rarely seen in cats and most of the reports
available are descriptions of individual cases (3). Affected
animals have hyperextensible and fragile skin (1,8). Delayed
wound healing has been reported to be a complication
of EDS in humans, using clinical and histologic criteria,
while wound healing in dogs and cats with EDS appears
to be similar to that of nonaffected animals (14). These
disorders are also referred to as dermatosparaxis or
cutaneous asthenia in animals (1). There is no therapy for
the disease, but consistent management can allow affected
cats to live long lives (8).
2. Case history
A 2-year-old, female, spayed crossbred cat, weighing 3.5
kg, was presented to the Department of Internal Medicine,
Faculty of Veterinary Medicine, İstanbul University,
with alopecia, loss of appetite, and hyperelasticity of the
skin (Figure 1). Anorexia was evident for 4 days and the
skin elasticity had been noted for 3 weeks. Generalized
*Correspondence: [email protected]
lymphadenopathy, an ulcerative wound on the left hind
leg (Figure 2), and hyperextensibility of the skin were the
abnormal findings detected on physical examination.
The rectal temperature was 38.4 °C and respiration rate
was 18 breaths/min. The diagnostic work-up included a
complete blood count, blood serum biochemistry panel,
and urinalysis to rule out any internal disease associated
with these skin lesions.
Mild leucocytosis (white blood cell count: 19.75 × 103
µL, reference range: 5.5–19.0) and hypoproteinemia (total
protein: 5.2 g/dL, reference range: 5.9–8.5) were detected.
Blood urea nitrogen (50 mg/dL, reference range: 15–34)
concentration was slightly increased. The rapid tests of
feline immunodeficiency virus (FIV), feline leukemia
virus (FeLV) (FIV Ab/FeLV Ag Test Kit Anigen, BioNote,
Inc., South Korea), and feline infectious peritonitis (FIP)
(FCoV Ab Test kit Anigen, BioNote, Inc., South Korea)
were found to be negative. Urinalysis findings were also
normal. Due to the presence of alopecia, the trace element
zinc was assayed by spectrophotometry and found to be
0.4 µg/mL, which was lower than the reference range (0.7–
2.0 µg/mL).
The biopsy areas were chosen randomly. Punch
biopsies (6 mm) of the lesional skin involving the left hind
leg and the sacrocaudal region were obtained from the cat
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DOKUZEYLÜL et al. / Turk J Vet Anim Sci
Figure 2. Ulcerative wound of the left hind leg.
Figure 1. Abnormal cutaneous laxity and hyperextensibility of
skin, clearly seen in trunk.
using local anesthesia and the biopsy sites were allowed
to heal by second intention. The biopsy samples were sent
to the Department of Pathology for histopathological
examination.
In an attempt to evaluate the collagen defect, a skin
extensibility examination was performed. The skin over the
dorsal lumbar region was stretched to the maximum point,
without causing any discomfort, and the measurement was
made carefully. The body length was measured from the
occipital crest to the base of the tail. The skin extensibility
index (SEI) was found to be increased by 22% than the
reference value described as 19% (2).
The examination of skin scrapings and hair plucks
did not reveal any parasites or mycotic infections.
Histological skin samples were fixed in neutral 10%
buffered formalin and routinely processed. Sections 5 μm
thick were stained with hematoxylin and eosin (H&E)
and Masson’s trichrome and were examined under light
microscope. Histopathologically, there was intense
neutrophilic infiltration, fibrosis, and necrosis in between
short and irregular collagen fibers. The neutrophilic
infiltration suggested a secondary inflammation process.
Focal lipocytic proliferation in the dermis (Figure 3),
irregular papillary structures, and fibroblastic hyperplasia
(Figure 4) in the epithelial layer were detected. There was
an increase in the number of fibrocytes around the hair
follicles and nest formations of fibroblasts were observed
246
in the sections stained with Masson’s trichrome. In some
cases the abnormal fibers appeared outlined by increased
numbers of fibroblast (5,7). In such cases, fibrocytes, which
are not noticeable in the papillary and reticular layers of
the normal dermis, have become visible. Fibrocytic and
fibroblastic hyperplasia were seen underlying the epithelial
layer and fibroblast cell increase and collagen deficiency
were detected (Figure 5). All these histopathologic findings
were compatible with feline cutaneous asthenia (15).
For electron microscopy, similar skin samples were
fixed in 4% paraformaldehyde, postfixed in osmium
tetroxide, and embedded in low-viscosity Spurr spin.
Ultrathin sections were cut, counterstained with 0.5%
uranyl acetate and lead citrate, and examined with a Zeiss
902A electron microscope. Electron microscopy revealed
an irregular, disorganized pattern and the decrease of
the collagen fibers (Figure 6). Normally, collagen fibers
constitute 70% of the proteins of the dermis. In contrast to
normal skin, diminished collagen fibers were seen in the
present case.
Initial therapy included saline infusion (20 mL/kg
intravenously (IV)) (Isotonic NaCl®, 500 mL, Eczacıbaşı
Baxter, Turkey), ceftriaxone disodium (Rocephine® IV
amp., 1 g, Roche, Turkey; 25 mg/kg, q12 h, IV), vitamin
C (Redoxon® IV amp., 500 mg/5 mL, Bayer, Turkey; daily
50 mg/kg, IV), dexpanthenol (Bepanthene® amp., 500
mg/2 mL, Roche, Turkey; 0.5 mL, 2 times every other
week, intramuscularly), and vitamin E (Ephynal®, 300 mg,
Bayer, Turkey; 300 IU/day, per os (PO)). The drugs were
applied for 10 days. Because of decreased appetite and
water consumption, serum infusion therapy was advised.
DOKUZEYLÜL et al. / Turk J Vet Anim Sci
Figure 3. Focal lipocytic infiltration on dermis, H&E, 4×. Bar:
200 µm.
An antibiotic was also given for mild leucocytosis and skin
lesions. Vitamin C, dexpanthenol, and vitamin E were
essential for a healthy skin. A protected environment was
recommended to the owner because of the hyperelasticity
of the skin.
The second referral happened 10 days after the first
referral. Blood was withdrawn for hematology and blood
serum biochemistry analyses. Leucocytosis was healed
and total protein was detected within normal ranges. With
this treatment, the appetite was increased and the mobility
was markedly improved. The sections of the skin where the
samples were taken had been healed completely, but the
hyperelasticity of the skin remained the same.
The therapy of the patient was continued with vitamin
C and zinc (Zinco-C tab.®, 15 mg, Berko, Turkey; 50 mg/
kg/day, PO) and vitamin E (Evicap® cap. 100 mg, Koçak
Pharma, Turkey; 100 IU/day, PO) for 1 month. Collagen
(hydrolyzed) (Collagen for Pets® tab., Alfa Natural
Company, USA) was also used once per day for 2 months.
The cat’s general condition status was good, including the
skin elasticity. The owners were instructed to continue
with the current vitamins, especially with vitamin C, for
6 months and to refer to our policlinic in the event of any
abnormal situations occurring.
The clinical picture and the histopathological findings
were compatible with feline cutaneous asthenia. Diagnosis
was made step by step as described above.
3. Results and discussion
The terms of cutaneous asthenia, dermatosparaxis, and
EDS denote a disease complex that includes several
hereditary congenital defects of dermal connective tissue
in man and in various animal species (5–10,12). Feline
cutaneous asthenia is a very rare, inherited disorder of
collagen production in cats. The clinical picture of the
Figure 4. Fibroblastic hyperplasia, H&E, 40×. Bar: 25 µm.
affected cat is characterized by skin hyperextensibility
and fragility, compatible with the signs and symptoms
described for cats with cutaneous asthenia (5–10, 12).
Due to the cat’s young age and its symptoms, the SEI
and histopathologic results were all compatible with a
congenital defect in the present case. Breed predispositions
of the individual animal species to asthenia are reported.
In cats, Himalayans and domestic shorthairs are the
predisposed breeds (2). In this report, our patient was
a mixed-breed household cat. Genetic analysis as a
diagnostic tool could not be performed as the patient was
a stray cat, found on the street while she was a kitten.
It is very unusual to see the complete syndrome
of cutaneous fragility, articular laxity, and ocular
abnormalities in the same animal. The cutaneous form
is the most commonly seen (12). In this patient, only the
cutaneous form of the disease was present. The SEI was also
higher (22%) than the reference value and the cutaneous
hyperextensibility was remarkable in this patient.
In the present case, morphologic changes were seen
in dermal collagen in light microscopic examination.
Collagen fibers showed alterations in arrangement and
length and were characterized by shortening, disarray,
curling, and uneven size. The disorganization of the
collagen fibrils is also a characteristic feature observed
in feline patients with EDS (7), as well as the findings of
disorganization of collagen fibrils on electron microscopy
(3,5,8,15). Cutaneous asthenia is a congenital form of feline
skin fragility syndrome (FSFS) that has also been reported
in young cats. Histologically, some cases of cutaneous
asthenia are difficult to distinguish from acquired skin
fragility with differentiation based on signalment, history,
and SEI. Histopathology of skin biopsies in FSFS reveals
marked epidermal and dermal atrophy although the skin
of the animals is not hyperextensible (16).
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DOKUZEYLÜL et al. / Turk J Vet Anim Sci
Figure 5. Fibroblast cell increase and collagen deficiency, H&E,
20×. Bar: 50 µm.
There is no specific treatment protocol for this
disease. In spite of any therapy, some authors suggest
the oral administration of vitamin C, which is necessary
for collagen synthesis in cats (50 mg/animal, daily) (2).
However, secondary manifestations of the disease, such
as joint laxity, must confer a more guarded prognosis
Figure 6. Electron micrograph of the dorsal scapular skin of
the cat. Irregular, disorganized pattern and decrease of collagen
fibers are clearly seen.
(2,6,17). Despite the poor prognosis, the patient must be
taken care of to avoid causing any skin injuries.
To the knowledge of the present authors, this is the first
report of cutaneous asthenia in cats or any other animal
species in Turkey.
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