86
Equine vet. Educ. (2004) 16 (2) 86-89
Special Article
Clinical use of triamcinolone acetonide in the horse (205 cases)
and the incidence of glucocorticoid-induced laminitis
associated with its use
M. J. MCCLUSKEY* AND P. B. KAVENAGH
Kavenagh & McCluskey Equine Clinic, 6 Tanner Street, Geelong, Victoria 3219, Australia.
Keywords: horse; triamcinolone; laminitis; glucocorticoid
Introduction
Glucocorticoids have been implicated as a cause of ‘steroid-
induced laminitis’ in horses for more than 25 years (Vernimb
et al. 1977; Lose 1980; Lawrence et al. 1985; Eustace and
Redden 1990; Harkins et al. 1993). It has previously been
observed that horses treated with triamcinolone are
particularly at higher risk of developing acute laminitis (Hood
et al. 1982). However, a causal link between corticosteroids
and laminitis in the horse has not been documented
(Lawrence et al. 1985).
In this report we present a retrospective,
uncontrolled study of the clinical use of triamcinolone as
triamcinolone acetonide (TMC) in 205 mature horses in a
3-person equine ambulatory clinic and the subsequent
incidence of laminitis associated with its use.
Materials and methods
Case records were retrieved from our clinic of all mature horses
treated with TMC (Kenacort-A 10 and Kenacort-A 40)1
between 1 July 1997 and 30 June 2001. Case subject details
examined included age, breed, sex, TMC dosage, frequency of
TMC use, disease treated and history of a diagnosis of laminitis.
Results
Two hundred and five cases in which TMC was used as a
therapeutic agent in mature horses were recorded. They
included 132 horses, of which 91 (68.9%) received a single
treatment with TMC and 41 (31.1%) received more than one
treatment with TMC.
Analysing the treatments on a case, rather than patient, basis
revealed there were 129 males (62.9%) (the vast majority of
whom were geldings), and 76 females (37.1%). Of the 205
cases, 183 (89.3%) were Thoroughbreds/Thoroughbred crosses,
*Author to whom correspondence should be addressed.
EQUINE VETERINARY EDUCATION
16 (7.8%) Standardbreds and 6 (2.9%) other breeds including
Clydesdales, Quarter Horses, Warmblood crosses and an Arab.
Ages ranged from 2 to 23 years with a mean and median
both of 5 years. One hundred and four cases (50.7%) received
40 mg TMC/treatment (62 male, 42 female). One hundred cases
(48.8%) received 80 mg TMC/treatment (67 male, 33 female)
and 1 (0.5%) case received a total body dose of 10 mg TMC.
The number of horses treated with TMC intra-articularly for
synovitis/osteoarthritis was 170 (82.9%), while 16 (7.8%)
received treatment intrathecally for tenosynovitis, 11 (5.4%)
subconjunctivally for uveitis, 2 (1%) intralesionally for localised
inflammation, 2 (1%) intrabursally for carpal hygroma, 2 (1%)
intramuscularly for pruritus, 1 (0.5%) intrabursally for a capped
hock and 1 (0.5%) intramuscularly for IAD (inflammatory airway
disease). Of the 41 horses treated on more than one occasion
with TMC, 25 received TMC on 2 occasions, 10 on 3 occasions,
3 on 4 occasions, 2 on 6 occasions and 1 on 10 occasions.
Out of the 205 cases, 4 (2%) were diagnosed with
laminitis. These 4 cases were seen in 4 different horses;
2 horses had been diagnosed as having laminitis on one
occasion prior to TMC but did not develop laminitis subsequent
to its use. The third horse developed laminitis 18 months after
TMC therapy and was found to be suffering from a post
foaling, toxaemic metritis at the time the diagnosis of laminitis
was made. Due to the time difference between treatment with
TMC and diagnosis of laminitis, no link was made between the
two. The fourth horse, a 7-year-old Thoroughbred gelding, was
diagnosed with laminitis one week after treatment with
40 mg intra-articular TMC for osteoarthritis (10 mg into each
of the left and right fore fetlock joints and the left and right
intercarpal joints). This horse had been diagnosed with laminitis
7 months previously. Due to the lack of response to treatment
of its osteoarthritis with other therapies, and concerns
regarding further administration of glucocorticoids, this horse
was retired from racing.
Of the 205 cases treated with TMC only, 1 (0.5%) was
found to have succumbed to laminitis in association with TMC
therapy and this horse had been treated for laminitis prior to
M. J. McCluskey and P. B. Kavenagh
receiving TMC. Of the 202 cases receiving TMC and not
previously having been diagnosed with laminitis, none
developed laminitis subsequent to treatment with high dose
TMC. Of the 3 horses that had laminitis prior to receiving TMC,
one (33.4%) developed laminitis subsequent to receiving TMC.
Discussion
Glucocorticoids are a family of corticosteroids affecting
protein, fat and carbohydrate metabolism and providing
powerful anti-inflammatory effects in the body. Cortisol is the
main naturally-occurring glucocorticoid; however, more
potent synthetic analogues with less mineralocorticoid activity
have been developed (Harkins et al. 1993). Triamcinolone
acetonide is one of these analogues and is used to treat a
variety of diseases in the horse, most commonly via the
intramuscular or intrasynovial route (French et al. 2000). It has
5 times more anti-inflammatory activity than cortisol and one-
fifth of the activity of betamethasone (Harkins et al. 1993).
In man, the recommended dose for TMC varies significantly
depending on the disease being treated. Suggested doses for an
adult include 10 mg intra-articular TMC for pain control after
arthroscopic knee surgery (Wang et al. 1998), 40 mg intra-
articular TMC for shoulder capsulitis (de Jong et al. 1998), 60 mg
i.m. TMC for pseudogout (Roane et al. 1997), 120 mg i.m. for
steroid-dependent asthma (Mancinelli et al.1997) and 360 mg
i.m. for severe, life-threatening asthma (Ogirala et al. 1996).
In contrast, the commonly recommended doses for TMC use
in the mature horse are much lower and include 5–15 mg
(Stashak 1987), up to 18 mg (Nixon 1992) and up to 20 mg
(Anon 1998; Moriello et al. 1998). When allowing for body mass
differences, these doses are lower than that used in humans on
a mg/kg basis by a factor of up to 60. Empirical evidence
regarding the triggering of laminitis in the horse is the main
reason higher doses are not recommended. However, no studies
have been published that show the dose or dosing regime of
TMC that is required to induce laminitis (French et al. 2000).
Also, field trials using triamcinolone have been performed which
have led to the observation that triamcinolone in and of itself did
not produce laminitis in the horse (Hood et al. 1982).
A number of studies have been reported where doses
greater than 20 mg TMC/horse were used. The effects of TMC
on pulmonary function, bronchoalveolar lavage cytological
features and serum cortisol concentrations were studied in
control horses and those with chronic obstructive pulmonary
disease. A total of 10 horses received i.m. TMC at a dose rate of
0.09 mg/kg bwt. This equates to approximately a 40 mg total
body dose for a 450 kg mature horse. None of these animals
were reported to show evidence of laminitis during a 16 week
follow-up period (Lapointe et al. 1993). In a study of the effects
of TMC on serum osteocalcin concentration, 10 mature horses
also received a dose of 0.09 mg/kg bwt i.m. No evidence of
laminitis was reported during a 5 month follow-up period
(Lepage et al. 1993). In a study on the pharmacokinetics and
metabolic effects of TMC, 5 mature horses were given
0.2 mg/kg bwt TMC i.v. dissolved in DMSO (equivalent to a dose
of 90 mg for a 450 kg horse) and also TMC i.m. at a dose rate
87
of 0.2 mg/kg bwt. No clinical evidence of laminitis was seen for
2–14 months after the experiment. However, laminar rings
developed in the hooves of 4 of the 5 horses (French et al.
2000). A dose of 40 mg TMC or methylprednisolone (MP) was
used intrabursally (navicular bursa) for the treatment of
navicular disease in 161 horses and in 50% of these horses both
forelegs were injected, equating to a total body dose of 80 mg
of glucocorticoid. While no mention was made of the
percentages of horses that received TMC vs. MP, of the
148 horses available for follow-up 12 months or more later,
none were reported to have suffered laminitis associated with
the use of TMC (Verschooten et al. 1990).
Doses of TMC higher than those currently recommended for
horses are routinely used in our practice and, from the data
presented, the risk of triggering glucocorticoid-induced laminitis
has, in our experience, been very small. In the 201 cases with no
known history of laminitis and that received either 40 or
80 mg doses of TMC, none (0%) were diagnosed with laminitis
linked to receiving treatment with TMC. As no long-term
follow-up assessment of the treated horses’ hooves was
undertaken, it is possible that growth defects (laminar rings)
may have developed in some of the cases subsequent to the use
of high doses of TMC, as previously reported (French et al.
2000). It is also possible that some of the horses may have
developed laminitis subsequent to their treatment with TMC
but did not receive veterinary attention. Considering the severity
of lameness usually seen with laminitis this was thought to be
unlikely. Why no cases of laminitis were encountered in normal
horses subsequent to the use of high dose TMC is unknown.
Because only a small number of horses received a significant
systemic load of TMC, this may have been a factor contributing
to our findings. The authors have been using doses of greater
than 20 mg TMC for a combined total of over 19 years. During
this period, neither author has experienced a single case of
glucocorticoid-induced laminitis in horses apart from the case
presented and, as already mentioned, this was diagnosed with
laminitis prior to receiving TMC.
In a controlled model of osteoarthritis in the horse, TMC has
been shown to exert a chondroprotective effect when used intra-
articularly. Compared to placebo, direct and remote site intra-
articular injection of 12 mg TMC into horses with a surgically-
created carpal osteochondral fragment produced favourable
effects on clinical lameness and on synovial fluid, synovial
membrane and morphological parameters of articular cartilage
(McIlwraith 2000). Unfortunately, despite the widespread use of
glucocorticoids including TMC in equine practice, no evaluation
of therapeutic doses (dose titration studies) has ever been done
with any of the intra-articular glucocorticoids used in the horse
(McIlwraith 1992). The anti-inflammatory drugs of choice for
treatment of heaves (RAO) are glucocorticoids. However,
concern over inadequate dosing with glucocorticoids due to the
possibility of development of laminitis has been expressed with
regard to the treatment of heaves (RAO) (Robinson et al. 2001).
Further studies are needed to provide information on the dose of
TMC that will be most clinically efficacious, while at the same
time minimising the chance of deleterious effects occurring, in
particular for intra-articular and intramuscular use.
88
Further work also needs to be carried out in determining
the dose and dosage regime of TMC that may induce laminitis
and the factors which may contribute to the likelihood of
laminitis occurring when using TMC in the horse. No conclusive
evidence exists to explain the mechanism of action by which
glucocorticoids may induce laminitis in the horse, but several
theories have been suggested. A direct effect of TMC on the
laminae is unlikely, as incubation of hoof explants with TMC
has failed to produce the classical lamellar separation normally
seen in laminitis (C. Pollitt, personal communication).
Betamethasone and hydrocortisone have been found to
significantly enhance contraction of digital arteries and
veins mounted in organ baths when the tissues had been
partially contracted by exposure to biological amines including
epinephrine, norepinephrine and serotonin. This
corticosteroid-potentiated vascular response of digital vessels
was suggested as a possible mechanism for the laminitropic
effects of glucocorticoids (Eyre et al. 1979). A follow-up study
using isolated feet, pump-perfused with oxygenated Kreb’s
saline, also found that the corticosteroids tested caused a
significant potentiation of the reactivity of the digital
vasculature to several endogenous amines. It was speculated
that this might then create venous obstruction in the digit and
represent a pharmacological basis for laminitis (Eyre and Elmes
1980). The process that initiates the destruction of the lamellar
attachment apparatus in laminitis begins to operate during the
developmental phase before the first clinical sign of laminitis is
apparent. Epidermal cell necrosis and intra-vascular necrosis
have, however, not been recognised in the developmental
stage of laminitis (Pollitt 1999). The theory of impeded blood
flow causing ischaemic necrosis of lamellar tissue as the
pathway for induction of laminitis has been contradicted by
experimental evidence showing increased rather than
decreased digital blood flow during the developmental phase
of laminitis (Robinson et al. 1976; Trout et al. 1990).
Dexamethasone and triamcinolone have been shown to
have significant mineralocorticoid properties as well as causing
a period of hypoadrenalism (Slone et al. 1983). These effects
have been suggested as a possible mechanism for their role in
predisposition to laminitis by one of 2 ways. First, the resulting
sodium retention leading to angio-oedema would enhance
vasoconstriction and hypertension. Second, the relative
hypoadrenal state may leave the animal unable to respond
properly to endotoxin release (Slone et al. 1981). Oedema has,
however, not been identified in the developmental stage of
laminitis. Instead, the appearance of freshly dissected laminitis
tissue is one of dryness, which is not characteristic of tissues
affected by a compartment syndrome. Also there is no
evidence to show that endotoxin release into the bloodstream
or peritoneal cavity will trigger laminitis (Pollitt 1999).
Recently, it has been suggested that alterations to glucose
metabolism may be a possible mechanism for development of
laminitis. Hoof explants remained intact for 8 days when
incubated in a glucose containing solution but separated
within 36 h when incubated in saline. The separation occurred
between the basal epidermal cells and their basement
membrane, which is characteristic of the hoof separation that
Clinical use of triamcinolone acetonide
occurs in laminitis. Addition of glucose to the saline prevented
the separation from occurring (Pass et al. 1998). When TMC is
given i.v. or i.m. to mature horses, it was found to induce a
prolonged period of hyperglycaemia, hyperinsulinaemia and
hypertriglyceridaemia. While not conclusive, it was suggested
that part of the hyperglycaemia was due to a reduction in
glucose utilisation by peripheral tissues. This may then
contribute to the development of TMC-induced laminitis
(French et al. 2000).
Another possible mechanism for glucocorticoid-induced
laminitis may be via the effects of glucocorticoids on intestinal
permeability. Glucocorticoids have been found to increase
gastroduodenal permeability in man (Kizilitas et al. 1998) and
small intestinal permeability in rats (Davies et al. 1994). Recent
evidence has implicated a Strep. bovis exotoxin produced in
the large bowel of the horse as an important trigger factor in
the pathophysiology of carbohydrate-induced laminitis.
During carbohydrate overload the mucosa of the hind gut is
damaged (Krueger et al. 1986), which may allow exotoxins to
enter the circulation and reach the lamellar basement
membrane. Here, they are believed to activate resident matrix
metalloproteinases (MMPs) within the lamellar structure. Once
activated, these MMPs can degrade key components of the
basement membrane leading to separation of the basement
membrane from the epidermal basal cells (Pollitt 1999;
Mungall et al. 2001). If glucocorticoids are capable of inducing
a significant increase in the intestinal permeability of the
horse, then it may be possible that sufficient streptococcal
exotoxin is absorbed into the vasculature to trigger laminitis in
certain individuals. As far as the authors are aware, no studies
have been undertaken to test this theory.
Glucocorticoids have anecdotally been considered to be
contraindicated in the treatment of equine laminitis (Eustace and
Redden 1990; May 1992). They have, however, been shown to
reduce the activity of MMPs (Pelletier et al. 1995; Coughlan et al.
1998). If the laminitropic effects of glucocorticoids are found to
be operating at the level of the bowel to trigger laminitis, then
regional limb perfusion of the equine digit using low doses of
glucocorticoid may prove to be of value in the treatment of
laminitis. Anecdotally, excellent results with marked reduction
of pain have been previously reported using intra-arterial infusion
of glucocorticoids for the treatment of laminitis (Roberts 1965).
In conclusion, while considerable anecdotal evidence exists
that supports a link between glucocorticoid use and the
triggering of laminitis, this case series of horses treated with
high-dose TMC (the majority of which had locally treated
conditions) provided no evidence to support the link between
TMC use and the induction of laminitis. In our experience, we
have found that higher doses of TMC than those currently
recommended can be used safely in the horse in certain
situations. More research needs to be conducted into what is the
best therapeutic dose of TMC when used both intramuscularly
and intrasynovially. At this stage, no conclusive evidence exists to
prove that glucocorticoids can induce laminitis in the horse.
Manufacturer’s address
1Bristol-Myers Squibb, Noble Park, Victoria, Australia.
M. J. McCluskey and P. B. Kavenagh
Acknowledgements
The authors’ would like to thank Dr John Hyland, Avenel Equine
Clinic, Avenel, Victoria, Australia, for reviewing this manuscript.
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