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Case report
Zonal dermal separation: a distinctive histopathological
lesion associated with hyperelastosis cutis in
a Quarter Horse
SABRINA H. BROUNTS,* ANN M. RASHMIR-RAVEN* and SHARON S. BLACK
*Animal Health Center and
Diagnostic Laboratory Services, College of Veterinary Medicine, Mississippi State University, Mississippi
State, Mississippi, USA
(Received 10 October 2000; accepted 10 February 2001)

Abstract This case report describes a distinctive deep cutaneous lesion in a 1-year-old Quarter Horse filly with
hyperelastosis cutis. The horse had a typical clinical presentation of hyperelastic skin associated with a 6-month
history of cutaneous wounds that developed following minor cutaneous trauma. Punch biopsies of skin from
the affected horse were thinner than similar biopsies from an age- and breed-matched control. Significant
microscopic lesions were not seen in cutaneous punch biopsies stained with haematoxylin and eosin and
Massons trichrome stains, but the ultrastructure of the dermis from the affected horse was characterized
by variation in collagen fibre diameter and loose packing of collagen fibres within bundles. The horse was
euthanized and necropsied, and full-thickness sections of skin were collected and examined microscopically.
Affected skin was of normal thickness; however, the deep dermis contained a distinctive horizontal linear zone
in which separation of collagen bundles resulted in the formation of large empty cleft-like spaces between the upper
and lower regions of the deep dermis. We suggest the term zonal dermal separation for this microscopic lesion.
Incisional full-thickness skin biopsies should be taken in suspected cases of equine hyperelastosis cutis because
punch biopsies may not obtain enough deep dermis to adequately represent pathological change in the skin of
horses with this disorder.
Keywords: connective tissue disease, equine, hereditary disease, hyperelastosis cutis, Quarter Horse.

INTRODUCTION
EhlersDanlos syndrome (EDS) in humans is a group
of diverse, inherited connective tissue disorders that
results from mutations in collagen genes, mutations in
genes which encode enzymes that modify collagens
and mutations in genes that encode other proteins that
affect the nature of extracellular matrix.1 More than 10
subtypes of EDS have been classified based on clinical,
genetic and biochemical characteristics, and most of
these subtypes clinically manifest hyperextensible
skin.2 Inherited connective tissue diseases with similarities to EDS have been identified in a variety of domestic
and laboratory animals.3,4
To date, reported cases of horses with hyperextensible
skin have involved Quarter Horses5 8 with the single
exception of an Arabian-cross horse.9 In the Quarter
Horse, hyperelastosis cutis is a poorly characterized,
autosomal recessive, connective tissue disorder expressed as hyperextensible, easily torn skin, and has also
Correspondence: Dr Sharon S. Black, Mississippi Veterinary Diagnostic Laboratory, 2531 N. West St, Jackson, MS 39216, USA. Fax:
+1-601-354-6097, E-mail: sblack@cvm.msstate.edu
2001 Blackwell Science Ltd

been referred to as EDS, cutaneous asthenia and dermatosparaxis.10,11 Hyperelastosis cutis affects males and
females equally, and is evident at or within several
months of birth.10,11 In the United States, it is seen
most often in Quarter Horses from cutting horse lines.11
Clinical lesions consist of solitary or multiple areas of
loose, fragile skin primarily on the dorsal body.11
Affected skin tears easily in response to minor trauma
and heals slowly.10,11 Healing may result in extensive
dermal scarring and poor quality skin.10 Diagnosis
is based on the presence of typical cutaneous lesions
in a young Quarter Horse.11 Prevention requires
minimizing cutaneous trauma and treatment consists
of wound management.10 Affected horses should not
be used for breeding.11
Histological changes in the skin of horses with
hyperelastosis cutis are not well documented; however,
thinning of the dermis, as well as thinning, fragmentation and disorientation of dermal collagen, have
been described.10,11 This report describes a distinctive
histopathological finding in the skin of a Quarter
Horse filly having hyperelastosis cutis and contributes
to the characterization of the histomorphological
appearance of skin lesions associated with this disease.
219

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S. H. Brounts et al.

Figure 1. The characteristic skin lesions of hyperelastosis cutis in a

1-year-old Quarter Horse filly.

CASE REPORT
History
A 1-year-old Quarter Horse filly was presented for
evaluation of abnormal skin and nonhealing cutaneous wounds of 6 months duration. Previous treatment
with systemic antibiotics, systemic corticosteroids and
topical wound dressings did not resolve the skin
lesions. According to the client, the horses lesions were
enlarging and seemed to be pruritic and painful. The
horse would traumatize her skin by rubbing against the
stall door. The horse could not be groomed because
minor cutaneous trauma contributed to the development of skin wounds. Although the horses sire, dam
and brother had no clinically apparent skin abnormalities, the authors received anecdotal reports of similar
skin lesions in distant relatives of this horse.
Clinical findings, diagnosis and outcome
Physical examination revealed the horse to be in good
general body condition. A chronic nonhealing skin
wound was present on her right front limb above the
coronary band. Skin lesions on the dorsum of the body
were 27 cm in width (Fig. 1). Healing skin lesions
on each side of the thorax and on the left lumbar area
were characterized by alopecic, dry, scaly, thickened
skin surrounding central areas of scar tissue. A more
recent lesion on the left hip consisted of a small, welldemarcated, roughly circular tear in the skin. Multiple
areas of skin having a palpably soft consistency but a
normal appearance were present over the dorsum from
the neck to the tail and on both sides of the rump. The
skin in these areas was easily elevated when pinched
(Fig. 2). When released, this skin formed a fold that
gradually flattened out as the skin returned to its normal position. The horse appeared uncomfortable when
the hyperelastic skin was manipulated. A provisional
diagnosis of hyperelastosis cutis was made, and the
horse was hospitalized for further evaluation. Punch
biopsies (6 mm in diameter) of the hyperelastic skin
lesions from the affected horse were taken under local
2001 Blackwell Science Ltd, Veterinary Dermatology, 12, 219 224

Figure 2. The skin was hyperextensible in some areas.

anaesthesia. Similar punch biopsies were taken from

the same locations on a breed- and age-matched control horse. Skin biopsies were immersion-fixed in 10%
neutral buffered formalin or Karnovskys fixative for
routine histopathology and electron microscopy,
respectively. Histopathological and ultrastructural
findings, described below, were consistent with a diagnosis of hyperelastosis cutis.
During 7 weeks of hospitalization with routine care,
the horse developed a large (20 40 cm) area of loose,
hyperelastic skin over the sacrum and left hip. Moderate numbers of white hairs were scattered in the hair
coat over healed skin wounds. The wound over the coronary band on her right front limb had not healed.
Because the horses skin disorder was presumably
genetic and not amenable to treatment, she was euthanized. A full necropsy was immediately performed, and
a complete set of tissues, including skin, was collected
for histopathological examination.
Biopsy and necropsy findings
Formalin-fixed punch biopsies of the skin were routinely processed, embedded in paraffin wax, sectioned
at 4-m thickness, mounted on glass microscope slides,
stained with haematoxylin and eosin (H&E) or Massons
trichrome stain, and examined under a light microscope. The total combined thickness of the epidermis
and dermis of the punch biopsies obtained from the
back and hip of the affected horse was 34 mm, in

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Hyperelastosis cutis in a Quarter Horse

221

Figure 3. Note the variability in diameter of collagen fibres in the

dermis (TEM; 54 000).

contrast to a thickness of 5 mm for skin biopsies from

similar sites on the control horse. No microscopic
lesions were noted in sections stained with H&E or
Massons trichrome.
Skin biopsies fixed in Karnovskys fixative for electron microscopy were washed in potassium hydroxide
buffer, postfixed in 2% osmium tetroxide, dehydrated
with graded ethyl alcohol and embedded in Spurrs
resin. Thin sections were placed on grids, stained with
uranyl acetate and lead citrate, and examined with a
JEOL 100 CXII transmission electron microscope.
Dermal collagen fibres exhibited a greater variation in
diameter in the affected horse (Fig. 3) than in the
control horse. The dermis of the affected horse also
contained scattered arrays of loosely packed collagen
fibres accompanied by mild accumulation of granular
material among the collagen fibres (Fig. 4).
At necropsy, the only significant gross lesions were
those of the skin. Full-thickness skin sections measuring 3 3 cm in width, and including underlying subcutaneous fat and muscle, were collected from multiple
sites including the thoracolumbar, sacral and coxofemoral regions. In some areas, the skin was very loosely
attached and easily slipped away from underlying
tissue when manipulated. In these areas, the skin
appeared to be held in place only by vessels passing
between the dermis and deeper tissues. There was no
evidence of accumulation of serous fluid or mucinous
ground substance in the skin. In order to maintain normal tissue orientation, the tissue sections were orientated with the epidermal surface up and affixed to
wooden tongue depressors prior to immersion fixation
in 10% neutral buffered formalin. Microscopic sections
were prepared and stained for histopathological examination as described.
The combined thickness of the epidermis and dermis
in microscopic slides of full-thickness sections of skin
from the back and hip was 5 and 6 mm, respectively.
A distinctive microscopic feature of sections of skin
obtained at necropsy was a horizontal linear zone of
loose collagen bundles located throughout the middle
of the deep dermis. Within this zone, there was variable
separation of collagen bundles and loss of dermal

Figure 4. Note the loosely packed collagen fibres in the dermis

(TEM; 13 400).

Figure 5. Zonal dermal separation throughout the middle of the

deep dermis (arrow) (H&E; 2.5).

density. In severely affected regions, the upper half of

the skin, including the epidermis, superficial dermis
and upper part of the deep dermis, was completely separated from the lower half of the deep dermis by an
empty, horizontal, cleft-like space through the middle
of the deep dermis (Fig. 5). Interstitial microhaemorrhage and increased vascularity of the middle region of
the deep dermis were also present. The haemorrhage
was acute in some sections; however, low numbers
of haemosiderin-laden macrophages indicated that microhaemorrhage was subacute to chronic in some sites
and did not occur secondary to perimortem cutaneous
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S. H. Brounts et al.

trauma. No additional abnormalities were revealed in

sections stained with Massons trichrome.

DISCUSSION
To date, the histopathological, ultrastructural and biochemical traits of equine hyperelastosis cutis have not
been well characterized. The most commonly reported
microscopic changes are thinning of the dermis and
fragmentation of collagen.10,11 In the horse in this
report, no significant microscopic abnormalities were
seen in the skin punch biopsies stained with H&E or
Massons trichrome stains, in contrast to a previous
report of hyperextensible, fragile skin in an Arabiancross filly, which described abnormal red cores in dermal collagen fibres stained with Massons trichrome.9
The full-thickness sections of skin revealed that
the dermis in this affected Quarter Horse contained a
distinctive horizontal linear zone of loose collagen
bundles throughout the middle of the deep dermis. This
region of loose collagen resembled that in previously
published photomicrographs of hyperelastosis cutis;11
however, in our case, the affected region of the dermis
appeared to be deeper and separation of collagen
bundles in this region resulted in the formation of large
empty cleft-like spaces with detachment of the upper
half of the skin from the lowermost part of the deep
dermis. There was no gross or light microscopy evidence of accumulation of fluid or ground substance in
the skin. Acute to chronic microhaemorrhage in the
deep dermis may have been a secondary effect of
trauma and mechanical shear on dermal blood vessels
resulting from excessive laxity of the skin. This is consistent with the occurrence of haematomas in some
horses with hyperelastosis cutis.10,11
In cutaneous punch biopsies from the affected horse
of this report, the decreased combined thickness of the
epidermis and dermis, in contrast to similar biopsies
from a control horse, was initially interpreted to be due
to either true thinning of the dermis in the affected
horse or a biopsy artefact. However, full-thickness sections of skin collected from the affected Quarter Horse
at necropsy were of normal thickness at 56 mm.
Average thickness of normal equine skin is reported to
be 4.6 mm (range 3.75.8 mm) in the lumbar region
and 5.5 mm (range 4.76.2 mm) in the sacral region.12
Therefore, we concluded that the cutaneous punch
biopsies from the affected horse were thinner because
the lower region of the deep dermis was not included in
the biopsy specimens due to separation of collagen
bundles. When examined by transmission electron
microscopy, the dermal collagen in the affected horse
exhibited variation in collagen fibre diameter as well
as loose packing of the fibres; these ultrastructural
features are similar to other reported cases of horses
with comparable skin lesions.6
In the horse in this report, cutaneous lesions
appeared associated with a distinct zone of altered dermal structure that could have only been detected by
2001 Blackwell Science Ltd, Veterinary Dermatology, 12, 219 224

deep incisional biopsy. A biochemical defect in one

component of the dermal connective tissue matrix may
affect the deposition and structure of other components to change the overall organization and mechanical properties of the dermis.13 Biochemical defects
identified in humans with EDS include fibronectin
defect, abnormal copper utilization with a defect in
lysyl oxidase, and abnormal collagen synthesis.1
Recently, tenascin-X deficiency was identified in a
human patient with EDS characterized by skin and
joint hyperextensibility, vascular fragility and poor
wound healing.14 Abnormalities in the organization
of collagen and dermal architecture that primarily
involve the collagen matrix are expressed phenotypically as an alteration of the entire interwoven pattern of
the dermis, as defects in the arrangement of fibrils into
fibres and fibre bundles, or as abnormalities in the size,
packing and relationships of fibre bundles; however,
increased or decreased elastin or amorphous ground
substance may also affect organization of collagen and
dermal architecture.15 Thorough characterization of
the structure and composition of normal equine skin,
as well as investigations of potential biochemical
abnormalities responsible for equine hyperelastosis
cutis, is needed.
We describe a distinctive deep dermal lesion in a
Quarter Horse with hyperelastosis cutis and suggest the
term zonal dermal separation for this histopathological finding. It remains to be proven if this lesion is a
common characteristic of equine hyperelastosis cutis.
We recommend that incisional full-thickness skin
biopsies be taken in suspected cases of hyperelastosis
cutis because punch biopsies may not obtain deep
dermis and adequately represent pathological change
in the skin of horses with this disorder.

ACKNOWLEDGEMENTS
The authors acknowledge the staff of Mississippi
State Universitys College of Veterinary Medicine and
Electron Microscope Center for technical assistance.
This is MAFES publication #J-9729.

REFERENCES
1. Byers, P.H. Inherited disorders of collagen gene structure
and expression. American Journal of Medical Genetics
1989; 34: 7280.
2. Byers, P.H. EhlersDanlos syndrome: recent advances
and current understanding of the clinical and genetic
heterogeneity. Journal of Investigative Dermatology
1994; 103 (Suppl.): 4752.
3. Minor, R.R., Wootton, J.A.M., Prockop, D.J. et al.
Genetic diseases of connective tissues in animals. Current
Problems in Dermatology 1987; 17: 199215.
4. Sinke, J.D., van Dijk, J.E., Willemse, T. A case of
EhlersDanlos-like syndrome in a rabbit with a review
of the disease in other species. Veterinary Quarterly 1997;
19: 1825.

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Hyperelastosis cutis in a Quarter Horse

5. Bridges, C.H., McMullan, W.C. Dermatosparaxis in
Quarter horses. Proceedings of the 35th Annual Meeting
of the American College of Veterinary Pathologists.
Toronto, Canada 1984: 12.
6. Hardy, M.H., Fisher, K.R.S., Vrablic, O.E. et al. An
inherited connective disease in the horse. Laboratory
Investigation 1988; 59: 253 62.
7. Lerner, D.J., McCracken, M.D. Hyperelastosis cutis in
2 horses. Journal of Equine Medicine and Surgery 1978; 2:
350 2.
8. Solomons, B. Equine cutis hyperelastica. Equine Veterinary
Journal 1984; 16: 541 2.
9. Gunson, D.E., Halliwell, R.E.W., Minor, R.R. Dermal
collagen degradation and phagocytosis. Occurrence in a
horse with hyperextensible fragile skin. Archives of
Dermatology 1984; 120: 599 604.
10. Pascoe, R.R.R., Knottenbelt, D.C. Manual of Equine
Dermatology. Philadelphia: W.B. Saunders, 1999:
146 7.

223

11. Stannard, A.A. Stannards illustrated equine dermatology

notes. Congenital diseases: epitheliogenesis imperfecta,
epitheliogenesis bullosa and hyperelastosis cutis. Veterinary
Dermatology 2000; 11: 21115.
12. Talukdar, A.H., Calhoun, M.L., Stinson, A.W. Microscopic
anatomy of the skin of the horse. American Journal of
Veterinary Research 1972; 33: 236590.
13. Holbrook, K.A., Byers, P.H. Structural abnormalities in
the dermal collagen and elastic matrix from skin of patients
with inherited connective tissue disorders. Journal of
Investigative Dermatology 1982; 79 (Suppl. 1): 7s16s.
14. Burch, G.H., Gong, Y., Liu, W. et al. Tenascin-X deficiency
associated with EhlersDanlos syndrome. Nature Genetics
1997; 17: 1048.
15. Holbrook, K.A., Byers, P.H., Pinnell, S.R. The structure
and function of dermal connective tissue in normal
individuals and patients with inherited connective tissue
disorders. Scanning Electron Microscopy 1982; (Part 4):
173144.

Rsum Ce cas clinique rapporte une lsion cutane profonde particulire chez un Quarter Horse g de 1 an
souffrant dhyperelastosis cutis. Le cheval a t prsent avec des lsions typiques de peau hyperlastique, associe
des pisodes de plaies cutanes apparaissant la suite de traumatismes mineurs depuis 6 mois. Les biopsies
cutanes de la peau de ce cheval taient plus fines que celles obtenues partir de contrles de mme ge et de
mme race. Aucune lsion microscopique na t observe sur les biopsies cutanes colores lhaematoxylineosine ou au trichrome de Masson, mais lultrastructure du derme montrait des variations du diamtre et des
anomalies de rpartition des fibres de collagne. Le cheval a t euthanasi et autopsi. De nouvelles sections
cutanes plus paisses ont t examines au microscope. La peau lse tait dpaisseur normale, mais le derme
profond prsentait une zone linaire horizontale dans laquelle une sparation des fibres collagniques provoquait
lapparition despaces vides, sparant le derme profond en deux zones. Nous proposons le terme sparation
dermique localise pour dnommer cette lsion microscopique. En cas de suspicion dhyperelastosis cutis chez
le cheval, des biopsies profondes sont ncessaires, car les biopsies au trpan ne prlvent pas toujours le derme
profond, et risquent de ne pas inclure ce type de lsion chez les chevaux atteints de cette maladie. [Brounts, S. H.,
Rashmir-Raven, A. M., Black, S. S. Zonal dermal separation: a distinctive histopathological lesion associated with
hyperelastosis cutis in a Quarter Horse. (Sparation dermique localise: une lsion histopathologique particulire
associe un hyperelastosis cutis chez un Quarter Horse.) Veterinary Dermatology 12: 219224.]
Resumen Este caso describe una lesin cutnea profunda especfica en un potro Quarter Horse de un ao con
hiperelastosis cutis. El caballo mostraba una presentacin clnica tpica de piel hiperelstica asociada a una
historia de seis meses de heridas cutneas que se producan tras leves traumatismos cutneos. Las biopsias por
punch del animal afectado eran ms delgadas que muestras similares de un control de la misma edad y raza. No
se observaron lesiones microscpicas significativas en biopsias cutneas por punch teidas con hematoxilina/
eosina y con tincin tricrmica de Masson, pero la ultraestructura de la dermis del caballo afectado se caracterizaba por variacin en el dimetro de las fibras de colgeno y una disposicin suelta de las fibras de colgeno en
los haces. El caballo fue eutanasiado y necropsiado, se realizaron secciones del total de grosor de las muestras
cutneas y se examinaron microscpicamente. La piel afectada era normal en grosor; sin embargo, la dermis profunda contena una zona linear horizontal destacada en la cual la separacin de los haces de colgeno provocaba
la formacin de espacios vacos en forma de grietas entre las zonas superficiales y profundas de la dermis. Sugerimos el trmino separacin dmica zonal para esta lesin microscpica. Se deberan tomar muestras cutneas
del total de grosor cutneo en casos sospechosos de hiperelastosis cutis equina ya que las biopsias por punch
pueden no obtener suficiente tejido drmico profundo para representar de forma adecuada las alteraciones
patolgicas en la piel de caballos con esta enfermedad. [Brounts, S. H., Rashmir-Raven, A. M., Black, S. S. Zonal
dermal separation: a distinctive histopathological lesion associated with hyperelastosis cutis in a Quarter Horse.
(Separacin drmica zonal: una lesin histopatolgica especfica asociada a la hiperelastosis cutis en un Quarter
Horse.) Veterinary Dermatology 12: 219224.]

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S. H. Brounts et al.
Zusammenfassung Dieser Fallbericht beschreibt eine tiefe Hautlsion bei einer einjhrigen Quarter Horse
Stute mit Hyperelastosis cutis. Das Pferd zeigte typische Befunde einer Hauthyperelastose sowie seit 6 Monaten
einen Vorbericht von kutanen Wunden als Folge von geringgradigen Hauttraumen. Hautbiopsiestanzproben
des betroffenen Pferdes waren dnner als Biopsien von einer Kontrolle gleichen Alters und gleicher Rasse.
Ausgeprgte mikroskopische Lsionen wurden in mit Hmatoxylin und Eosin und mit Masson-Trichrom
angefrbten Hautbiopsiestanzproben nicht gesehen, aber die Feinstruktur der Dermis des betroffenen Pferdes
war durch unterschiedliche Kollagenfaserdurchmesser und lose Anordnung der Kollagenfasern innerhalb der
Bndel gekennzeichnet. Das Pferd wurde eingeschlfert und obduziert, und Hautproben wurden genommen und
mikroskopisch untersucht. Die betroffene Haut war von normaler Dicke, allerdings enthielt die tiefe Dermis eine
deutliche horizontale, lineare Zone, in der eine Separierung der Kollagenbndel zur Bildung grosser, leerer,
spaltenhnlicher Rume zwischen den oberen und unteren Regionen der tiefen Dermis fhrte. Wir schlagen
fr diese mikroskopische Lsion die Bezeichnung zonale dermale Separierung vor. Inzisionsbiopsien sollten in
Verdachtsfllen von Hyperelastosis cutis des Pferdes genommen werden, weil bei Stanzbiopsien vielleicht nicht
genug von der tiefen Dermis entnommen wird, um ausreichende pathologische Vernderungen in der Haut von
Pferden mit dieser Erkrankung darzustellen. [Brounts, S. H., Rashmir-Raven, A. M., Black, S. S. Zonal dermal
separation: a distinctive histopathological lesion associated with hyperelastosis cutis in a Quarter Horse. (Zonale
dermale Separierung: Eine ausgeprgte histopathologische Lsion der Hyperelastosis cutis bei einem Quarterhorse.)
Veterinary Dermatology 12: 219224.]

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