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No evidence that therapeutic systemic corticosteroid
administration is associated with laminitis in adult
horses without underlying endocrine or severe
systemic disease.
A Knowledge Summary by
Catherine McGowan BVSc MACVSc DEIM DipECEIM PhD FHEA MRCVS 1*
Daniel Cooper BVSc MRCVS 2
Joanne Ireland BVMS PhD CertAVP(EM) MRCVS 3
1 University of Liverpool
2 Clent Hills Equine LLP
3 Animal Health Trust
* Corresponding Author (c.m.mcgowan@liv.ac.uk)
ISSN:
2396-9776
Published:
25 Jan 2016
in:
Vol 1, Issue 1
DOI:
http://dx.doi.org/10.18849/ve.v1i1.12.g19
Next Review Date:
26 May 2017
KNOWLEDGE SUMMARY
Question
In reported cases of iatrogenic laminitis in adult horses and ponies, is therapeutic administration of systemic
corticosteroid associated with the onset of laminitis?
Clinical scenario
Horses have been reported to develop laminitis following therapeutic systemic corticosteroid
administration and the risk of laminitis induced by administration of exogenous glucocorticoids
remains a
contentious issue in equine medicine. Previously the lack of reported adverse reactions to corticosteroids has
been cited as evidence to suggest no association with laminitis. Additionally,
many studies investigating the
use of corticosteroids in treatment of various conditions (such
as recurrent airway obstruction and
musculoskeletal disorders) have not observed induction of
laminitis.
It has been suspected that the development of laminitis following corticosteroid therapy is more likely in
horses with an underlying disease that causes laminitis, specifically, Systemic Inflammatory Response
Syndrome (SIRS) or severe systemic disease and endocrine disease. Johnson et al suggest that most widely
recognised form of endocrinopathic laminitis occurs in association with steroid administration and that use
of corticosteroids must be measured against the well-recognised risk of complicating laminitis (Johnson et al
2004). Johnson et al also state the likelihood of laminitis appears to be greater with the more potent agents
such as triamcinolone laminitis (Johnson et al 2004), while an earlier review suggests the association with
laminitis has not been reported for use of prednisone or prednisolone (Johnson et al 2002).
Early in vitro research demonstrated corticosteroid potentiation of the vasoconstrictor actions of
catecholamines and serotonin, suggesting the resulting venous obstruction on the hoof may cause laminitis
(Eyre & Elmes 1980). Skin perfusion was decreased in a study using six days of daily dexamethasone and
the authors suggested perfusion to the hoof may also be reduced, increasing
the risk of laminitis (Cornelisse
et al 2006). Following a standard overnight dexamethasone suppression test, non-obese ponies with a
history of prior laminitis showed elevated insulin
concentration and exaggerated production of insulin in
response to corticosteroids compared to control ponies (Bailey et al 2007). After a single administration of
triamcinolone, one study reported a prolonged period (3 – 4 days) of hyperglycaemia, hyperinsulinaemia and
hypertriglyceridaemia (French et al 2000). Additionally, four of the five horses in this study developed laminar
rings without clinical laminitis (French et al 2000). In a small cross-over study, healthy horses
demonstrated marked insulin resistance following alternate day dexamethasone administration for three
weeks
(Tiley et al 2007; Tiley et al 2008). Insulin resistance is associated with a predisposition to laminitis
Clinical bottom line
•
There is currently no conclusive evidence to support a causal association between
therapeutic
systemic corticosteroid administration and the development of laminitis
in healthy adult
horses/ponies.
•
There is weak evidence of an association between administration of multiple dos-
es of systemic
corticosteroid and the onset of laminitis in adult horses/ponies with
underlying endocrine
disorders or severe systemic disease.
Veterinary Evidence
ISSN: 2396-9776
Vol 1, Issue 1
DOI:
http://dx.doi.org/10.18849/ve.v1i1.12.g19
next review date: 26 May 2017
page | 2
total pages: 17
(McGowan 2008); therefore it is possible that glucocorticoid-induced decrease in insulin sensitivity may
increase the risk for development of laminitis.
Although these studies demonstrate pathophysiological effects of exogenous steroid administration which offer
plausible mechanisms by which corticosteroids may induce laminitis, particularly in those animals with
existing predisposing factors, they do not provide sufficient evidence to support the hypothesis of increased
risk of laminitis associated with the use of steroids in clinical practice. Therefore, this knowledge summary
aimed to identify cases of iatrogenic equine laminitis following
systemic administration of corticosteroids and
to appraise the evidence linking corticosteroid administration and laminitis onset.
The evidence
Thirteen publications, reporting a total of 40 iatrogenic cases of laminitis following systemic
corticosteroid administration, were identified in the literature searches (summarised in Table 1). These
comprised six single case reports, three case series, one non-randomised clinical trial of
dexamethasone
for the treatment of chronic respiratory disorders, a database of adverse drug
events, a journalistic style
anecdotal case report and a court case transcript. Included publications
were of level 4 (case series) or level
5 (mechanism-based reasoning) (OCEBM Levels of Evidence Working Group). Only one observational
study aimed to evaluate the prevalence of laminitis amongst horses treated with triamcinolone
(McCluskey & Kavenagh 2004). No experimental studies investigating the frequency of laminitis following
therapeutic corticosteroid administration
were identified.
Three publications (including eight cases) did not report information regarding the type of
corticosteroid
administered (Cripps & Eustace 1999; Lose 1980; Slater et al 1995). Of the 32 cases of iatrogenic laminitis
reported in the other included publications, 53% (n=17) were reported to occur following administration
of triamcinolone (Cohen & Carter 1992; McCluskey & Kavenagh 2004; Ryu et al 2004; U.S. FDA), 34%
(n=11) were reported to occur following administration of dexamethasone (Fredrick & Kehl 2000; Humber
et al 1991; Muyelle & Oyaert 1973; Vandenabeele et al 2004; U.S. FDA), 3% (n=1) occurred following
administration of methylprednisolone (U.S. FDA) and 3% (n=1) occurred following administration of
betamethasone (U.S. FDA). Two further cases were reported to develop laminitis following the
administration of more than one corticosteroid (Anon 2005; Winfield et al 2013).
Ten publications (including 14 cases) reported some information regarding duration of treatment or number
of corticosteroid treatments, of which 79% of cases (n=11/14) developed laminitis following multiple
doses of corticosteroid (Cohen & Carter 1992; Fredrick & Kehl 2000; Humber et al 1991; Muyelle & Oyaert
1973; Ryu et al 2004; Vandenabeele et al 2004; Winfield et al 2013). The remaining 21% of cases (n=3/14)
developed laminitis following administration of corticosteroid on a single occasion; however two of these
cases received multiple intra-articular doses of unknown corticosteroid (Lose 1980) or triamcinolone
(McCluskey & Kavenagh 2004) and the other case received multiple doses of dexamethasone and possibly
multiple intra-articular doses of
triamcinolone (Anon 2005).
Veterinary Evidence
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total pages: 17
Summary of the evidence
Muylle (1973)
Population:
10 normal horses and 15 horses with chronic respiratory disorders.
Respiratory cases referred to veterinary medical teaching hospital,
Ghent, Belgium
Sample size:
•
25 horses (predominantly Standardbreds and hunter type)
• 15 horses administered dexamethasone
• Study population included 2 iatrogenic laminitis cases
Intervention details:
Intramuscular administration of dexamethasone 25 mg on alternate
days for 4 – 6 treatments until remission of clinical signs achieved.
Study design:
Non-randomised, controlled clinical trial of dexamethasone for the
treatment of chronic respiratory disorders
Outcome studied:
Objective assessment: Lung function test results in horses with
chronic respiratory disorders compared to healthy controls and
following dexamethasone treatment.
Main findings:
(relevant to PICO question):
• 2 of the 15 dexamethasone-treated horses developed
laminitis ‘a short time after discharge’.
• 1 of the 2 laminitis cases was treated successfully
Limitations:
• Primary objective of the study was investigation of lung
function in response to dexamethasone treatment for
chronic respiratory disease.
• No clinical details presented for iatrogenic cases and
corticosteroid administration not evaluated as risk factor for
development of laminitis.
• Lack of temporal information precludes assessment of
association between corticosteroids and onset of laminitis.
Lose (1980)
Population:
2 year old Standardbred colt attended by a first opinion equine
hospital, Pennsylvania, USA
Sample size:
1
Intervention details:
Single intra-articular administration both tarsi. Corticosteroid and
dose not reported.
Study design:
Case report
Outcome studied:
Objective assessment: Description of treatment of single iatrogenic
laminitis case
Main findings:
(relevant to PICO question):
•
Onset of laminitis affecting all four feet 8 days after
corticosteroid administration. Confirmed by radiography –
rotation evident in all four feet (right fore most severely
affected).
• No clinical details or information regarding diagnostic testing
for underlying disease(s) reported.
Veterinary Evidence
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Limitations:
•
Single case report, with primary focus on treatments used
for laminitis.
• Provides weak evidence of association between therapeutic
administration of corticosteroids and onset of laminitis in a
single horse. No details presented regarding presence or
absence of underlying disease.
Humber (1991)
Population:
2 horses with immune-mediated thrombocytopaenia referred to
veterinary medical teaching hospital, Pennsylvania, USA
Sample size:
1 iatrogenic laminitis case (8 year old Thoroughbred mare)
Intervention details:
Intravenous administration of dexamethasone. 0.16mg/kg every 12
hours for 3 days
Study design:
Case report
Outcome studied:
Objective assessment: Description of clinical presentation and
treatment of immune-mediated thrombocytopaenia
Main findings:
(relevant to PICO question):
• Onset of mild laminitis affecting all four feet 10 days after
cessation of corticosteroid administration. Confirmed by
post mortem examination – slight displacement of the third
phalanx in both forelimbs.
• Affected horse had evidence of systemic disease
(progressive epistaxis, ecchymotic haemorrhages involving
the oral mucous membranes, hyphema, petechial
haemorrhages on the sclerae, and nasal and vaginal mucous
membranes). The horse also had swellings in the mid cervical
region over the jugular veins. Mucous membranes were
pale.Mild neutrophilic leucocytosis, anaemia,
hypoproteinaemic and thrombocytopenic. Blood in faeces.
Limitations:
• Single case report.
• Provides weak evidence of association between therapeutic
administration of systemic corticosteroids and onset of
laminitis in a single horse with severe systemic disease.
Cohen (1992)
Population:
10 year old Quarter Horse gelding referred to veterinary medical
teaching hospital, Texas, USA
Sample size:
1
Intervention details:
12mg (6ml) of triamcinolone administered; 2nd treatment 3 weeks
later of 10mg (5ml) of triamcinolone (injected by owner without
veterinary consult); 3rd treatment administered by owner 7 days
after 2nd second treatment (dose details unknown but suspension
was much stronger (40mg/ml)).
Study design:
Case report
Outcome studied:
Objective assessment: Description of clinical presentation and
treatment of steroid hepatopathy
Veterinary Evidence
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Main findings:
(relevant to PICO question):
•
Onset of bilateral forelimb laminitis 6 weeks and 6 days after
first corticosteroid administration (2 weeks and 6 days after
last). Confirmed by radiography – rotation evident in both
fore feet.
• Affected horse had evidence of severe concurrent disease
(hepatopathy and hyperadrenocorticism).
Limitations:
•
Single case report.
• Laminitis developed approximately 3 weeks following
cessation of corticosteroid treatment, which does not
convincingly support a causal association.
Slater (1995)
Population:
Laminitis cases attended by 7 private practices and referred to
veterinary medical teaching hospital, Texas, USA
Sample size:
•
108 laminitis cases
• Study population included 3 iatrogenic laminitis cases
Intervention details:
No details regarding corticosteroid administered, dose or duration of
treatment. 3 cases in series reported to have received steroids ‘just
prior to the onset of laminitis’ with no time frame stated.
Study design:
Case control study
Outcome studied:
Objective assessment: Horse level and clinical factors associated
acute or chronic laminitis and description of treatments
administered
Main findings:
(relevant to PICO question):
3 of 108 laminitis cases had a history of corticosteroid administration
prior to the onset of clinical signs.
Limitations:
• No clinical details presented for iatrogenic cases and
corticosteroid administration not evaluated as risk factor for
development of laminitis.
• Lack of temporal information precludes assessment of
association between corticosteroids and onset of laminitis.
Cripps (1999)
Population:
Laminitis cases referred to a specialist equine laminitis referral
centre, England, UK
Sample size:
• 216 laminitis cases, of which 211 included in study
•
Study population included 4 iatrogenic laminitis cases
Intervention details:
No details regarding corticosteroid administered, dose or duration of
treatment. 4 laminitis cases in series reported as iatrogenic
‘following injections of corticosteroids’ with no time frame stated.
Study design:
Case series – retrospective review of clinical records
Outcome studied:
Objective assessment: Horse level and clinical factors associated
with outcome of treatment for laminitis (successful versus
unsuccessful treatment)
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Main findings:
(relevant to PICO question):
4 laminitis cases in series reported as iatrogenic. 2 of the 4 iatrogenic
cases were treated successfully.
Limitations:
•
Primary objective of the study was investigation of clinical
parameters associated with outcome of treatment for
laminitis.
• No clinical details presented for iatrogenic cases and
corticosteroid administration not evaluated as risk factor for
development of laminitis.
• Lack of temporal information precludes assessment of
association between corticosteroids and onset of laminitis.
Frederick (2000)
Population:
23 year old American Saddlebred gelding, USA
Sample size:
1
Intervention details:
Single bolus injection of Naquasone (trichlormethiazide 10 mg and
dexamethasone acetate 0.55 mg/ml) followed by 4 days oral
administration of Naquasone tablets. Dose not reported.
Study design:
Case report
Outcome studied:
Subjective assessment: Owner and veterinary surgeon account of
single iatrogenic laminitis case
Main findings:
(relevant to PICO question):
• Onset of laminitis affecting all four feet on 4th day of
corticosteroid administration. Confirmed by radiography –
rotation evident in both fore feet.
• Gelding was obese with regional adiposity (cresty neck).
• Diagnostic tests for hypothyroidism and PPID inconclusive
(neither specific tests nor results reported).
Limitations:
• Very low quality non-peer reviewed single case report in
journalistic style.
• Provides very weak evidence of association between
therapeutic administration of systemic corticosteroids and
onset of laminitis in a single aged horse with clinical signs of
underlying endocrine disease
Veterinary Evidence
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total pages: 17
Ryu (2004)
Population:
3 year old Thoroughbred filly referred to equine hospital, Korea
Sample size:
1
Intervention details:
Intramuscular administration of triamcinolone acetonide 20 mg once
daily for 10 consecutive days
Study design:
Case report
Outcome studied:
Objective assessment: Description of clinical presentation and
treatment of single iatrogenic laminitis case
Main findings:
(relevant to PICO question):
• Onset of bilateral forelimb laminitis 33 days after first
corticosteroid administration (23 days after last).
• Confirmed by radiography – severe rotation evident with
eventual sole penetration.
• Initially referred 25 days after first corticosteroid
administration for haematuria and steroid hepatopathy with
weight loss, vaginal hyperaemia, leukopenia and polyuria.
• Affected horse had evidence of systemic disease (pyrexia,
tachycardia, tachypnoea), congested mucous membranes,
thrombophlebitis and neutrophilia).
Limitations:
• Single case report.
• Laminitis developed 23 days following cessation of
corticosteroid treatment, which does not convincingly
support a causal association.
McCluskey (2004)
Population:
Adult horses treated with triamcinolone in an equine ambulatory
practice, Victoria, Australia
Sample size:
• 132 horses treated with triamcinolone (total 205 triamcinolone
treatments).
• Study population included 1 iatrogenic laminitis case (7 year
old Thoroughbred gelding)
Intervention details:
Intra-articular administration of triamcinolone acetonide 10 mg into 4
joints (40 mg total dose)
Study design:
Case series – retrospective review of clinical records
Outcome studied:
Objective assessment: Prevalence of laminitis in adult horses treated
with triamcinolone
Main findings:
(relevant to PICO question):
• Single horse (n=1/132) developed laminitis one week after
corticosteroid treatment.
• Iatrogenic laminitis case reported to have previous episode of
laminitis 7 months prior. No clinical details or information
regarding diagnostic testing for underlying disease(s)
reported.
Limitations:
• Single case described within a case series with very limited
clinical data reported.
• Provides weak evidence of association between therapeutic
administration of systemic corticosteroids and onset of
laminitis in a single horse with previous history of laminitis.
Veterinary Evidence
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. Vandenabeele (2004)
Population:
Pemphigus foliaceus cases referred to a veterinary medical teaching
hospital, California, USA
Sample size:
•
20 pemphigus foliaceus cases
• Study population included 4 iatrogenic laminitis cases: 2 year
old Quarter Horse filly; 3.5 year old Quarter Horse filly; 4
year old Standardbred mare; 5 year old Quarter Horse
gelding
Intervention details:
• Oral dexamethasone 0.05-0.1 mg/kg per day (n=13); Oral
prednisone 1-2 mg/kg per day (n=3). Oral prednisolone 1-2
mg/kg per day (n=4)
• Duration of treatment not reported; however alternate-day
dosing of corticosteroids was implemented when lesions
were in remission (10–14 days of treatment)
Study design:
Case series – retrospective review of clinical records
Outcome studied:
Objective assessment: Description of clinical presentation and
treatment of pemphigus foliaceus cases
Main findings:
(relevant to PICO question):
• 4 iatrogenic acute laminitis cases reported following
dexamethasone treatment.
• 3 cases euthanased due to laminitis. 4th case treated
successfully.
• Serum albumin measured in 2 of the 3 non-surviving cases –
both had hypoalbuminaemia.
• Time frame of onset of laminitis relative to dexamethasone
not reported.
Limitations:
• 4 laminitis cases described with very limited clinical data
reported.
• Lack of temporal information precludes assessment of
association between corticosteroids and onset of laminitis.
. Anon (2005)
Population:
14 year old mare, England, UK
Sample size:
1
Intervention details:
• Dosage and nature of corticosteroids administered
contested ad unclear.
• Possible intra-articular administration of triamcinolone
acetonide both tarsi (1 x 80mg/2ml in each joint) OR intra-
articular administration of dexamethasone both tarsi (1 x
4mg in each joint)
• Multiple intra-muscular injections into back cumulatively of
20mg of dexamethasone
Veterinary Evidence
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Study design:
Court case transcript
Outcome studied:
Subjective assessment: Transcript of summary of evidence given
during court case
Main findings:
(relevant to PICO question):
• Laminitis diagnosed 11 days after corticosteroid treatment.
• Euthanased due to laminitis 61 days post-diagnosis.
• Received intra-articular administration of triamcinolone
right fore fetlock 4 years previously – dose not reported – no
adverse events. Received multiple intra-articular and intra-
muscular injections of dexamethasone 2 years – dose not
reported – no adverse events.
Limitations:
• No clinical details or diagnostic information reported.
• Court case assumes causal association between
administration of corticosteroids and onset of laminitis.
• Provides weak evidence of association between therapeutic
administration of large doses of corticosteroids and onset of
laminitis in a single horse. No details presented regarding
presence or absence of underlying disease.
. Center for Veterinary Medicine Cumulative Adverse Drug Event (ADE)
Population:
Adverse drug event (ADE) data from all reports received on paper by
the U.S. Food and Drug Administration Center for Veterinary
Medicine between 1987 and April 30, 2013, USA
Sample size:
• 106 cases of equine laminitis reported as ADE
• Included 19 cases of laminitis reported as ADE following
corticosteroid administration
Intervention details:
Not reported
Study design:
Not applicable – database of reported ADEs
Outcome studied:
Subjective assessment: Laminitis reported as ADE, by either
veterinary surgeons or horse owners
Main findings:
(relevant to PICO question):
Laminitis reported as ADE following administration of:
• Parenteral betamethasone (n=1);
• Oral dexamethasone (n=2);
• Parenteral dexamethasone (n=1);
• Parenteral methylprednisolone(n=1)
• Parenteral triamcinolone (n=13)
• Triamcinolone – route of administration unknown (n=1)
Limitations:
• No clinical details or diagnostic information reported;
therefore iatrogenic laminitis cases not confirmed.
• Lack of temporal information precludes assessment of
association between corticosteroids and onset of laminitis.
Veterinary Evidence
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. Winfield (2013)
Population:
9 year old Welsh pony stallion referred to a veterinary medical
teaching hospital, California, USA
Sample size:
1
Intervention details:
Intramuscular administration of dexamethasone (0.05 mg/kg once
daily for 3 consecutive days, followed by oral prednisolone (0.5-1.0
mg/kg once daily; plus topical administration of 0.015%
triamcinolone acetonide spray
Study design:
Case report.
Outcome studied:
Objective assessment: Description of clinical presentation and
treatment of a single pemphigus vulgaris case
Main findings:
(relevant to PICO question):
• Onset of laminitis affecting all four feet within 4 months
following initiation of corticosteroid administration (possibly
after 6 weeks of treatment based on Figure S5 legend in
supplementary information). Initial foot soreness developed
as prednisolone dose was increased to 0.8 mg/kg/day.
Confirmed by post mortem examination – rotation and hoof
wall separation in all four feet.
• In addition to pemphigus vulgaris, affected pony had
evidence of chronic inflammation and systemic illness,
considered by the authors to be contributing factors in the
development of laminitis.
Limitations:
• Primary objective of the report was to describe the clinical,
histological and immunological findings of a case of
pemphigus vulgaris.
• Lack of accurate temporal information precludes assessment
of association between corticosteroids and onset of
laminitis.
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Appraisal, application and reflection
The aim of this knowledge summary was to critically appraise published evidence of iatrogenic
equine
laminitis following systemic administration of corticosteroids. It was beyond the scope
of this review to
evaluate the extensive published literature reporting on the therapeutic use of
systemic corticosteroids
where laminitis has not been observed or reported as an adverse event
following treatment.
The 13 included publications were predominantly descriptive studies and provided low level
evidence
pertaining to the potential association between therapeutic administration of systemic corticosteroid and
the onset of laminitis (OCEBM Levels of Evidence Working Group). No studies of an appropriate design to
determine the incidence of laminitis following corticosteroid treatment or evaluate temporal relationships
between corticosteroid administration and the onset of laminitis
(i.e. longitudinal analytical studies) were
identified.
The only observational study investigating iatrogenic laminitis following treatment with
triamcinolone reported a prevalence of 0.8% (n=1/132; 95% confidence interval 0 – 2.2%) (McCluskey
& Kavenagh 2004). In the same study, three other cases of laminitis were reported, of which two were
diagnosed with laminitis prior to triamcinolone but did not develop laminitis subsequent
to its use.
Therefore, laminitis following triamcinolone administration was observed in 33% of horses with a previous
history of laminitis (n=1/3). The third horse developed laminitis 18 months after triamcinolone therapy as a
result of post foaling toxaemic metritis (McCluskey & Kavenagh
2004). Of 106 equine laminitis cases
reported as adverse drug events over a 26 year period, 18% (n=19) were attributed to corticosteroid
treatment, whereas 35% of cases (n=37) were attributed to administration of anthelmintics and 32% (n=34)
were reported following treatment with antibiotics or antiprotozoals (U.S. FDA).
Only eight publications (each reporting a single case of iatrogenic laminitis) provided information regarding
the time of onset of laminitis relative to corticosteroid administration (Anon 2005; Cohen & Carter
1992; Fredrick & Kehl 2000; Humber et al 1991; Lose 1980; McCluskey & Kavenagh 2004; Ryu et al 2004;
Winfield et al 2013). One of the eight cases occurred during corticosteroid treatment (onset of laminitis
reported on day 4 of a 5 day course) (Fredrick & Kehl 2000). Onset or diagnosis of laminitis was reported to
occur 7 days (McCluskey & Kavenagh 2004), 8 days (Lose 1980), 10 days (Humber et al 1991), 11 days (Anon
2005), 20 days (Cohen & Carter 1992) and 23 days (Ryu et al 2004) after cessation of corticosteroid
treatment. Two of these cases, one with severe systemic disease (Ryu et al 2004) and one with
hepatopathy and hyperadrenocorticism (Cohen & Carter 1992), occurred three weeks after the last dose
of corticosteroid. The longer the period of time between drug administration and disease onset, the less
likely the drug was a contributing factor in the aetiology due to its reduced efficacy in the body as time
passes (Harkins et al 1993). The time frame for both these two cases appears to be too long to suggest a
direct causal association, especially as in both cases laminitis occurred over a week after the onset of
clinical signs of systemic disease. In the remaining case, laminitis was reported to have occurred within 4
months of commencing corticosteroid treatment (Winfield et al 2013).
Seven publications provided diagnostic information, of which five (representing eight cases) reported
confirmation of diagnosis via radiography (Cohen & Carter 1992; Cripps & Eustace 1999; Fredrick &
Kehl 2000; Lose 1980; Ryu et al 2004) and two (representing two cases) reported confirmation via gross
pathology at post mortem examination (Humber et al 1991; Winfield et al 2013). Few included studies
provided detailed clinical information regarding the presentation and severity of laminitis. Two
epidemiological studies of laminitis (Cripps & Eustace 1999; Slater et al 1995) did not include any clinical
information pertaining to iatrogenic laminitis cases, and reported only that animals had received
corticosteroids prior to the onset of laminitis, while the Center for Veterinary Medicine Cumulative Adverse
Drug Event (ADE) Summaries Report (U.S. FDA) provided no details other than the type of corticosteroid
administered prior to laminitis. Where reported, laminitis most frequently affected all four feet (67%,
Veterinary Evidence
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n=4/6) (Fredrick & Kehl 2000; Humber et al 1991; Lose 1980; Winfield et al 2013), and a further two cases
(33%, n=2/6) (Cohen & Carter 1992; Ryu et al 2004) developed bilateral forelimb laminitis. Outcome was
reported for 18 cases, of which 50% (n=9) were reported to have survived/recovered, although two cases
were reported to have been retired from their previous athletic use due to laminitis (McCluskey & Kavenagh
2004; Ryu et al 2004). One non-surviving case was euthanased due to progression of pemphigus vulgaris
rather than laminitis (Winfield et al 2013) and the reason for euthanasia was unclear in one further non-
surviving case (Humber et al 1991).
Diagnostic evaluation of underlying disease(s) was infrequently reported. Of the five laminitis cases occurring
during treatment or within two weeks of corticosteroid administration, one horse was obese with marked
regional adiposity, suggestive of equine metabolic syndrome (Fredrick & Kehl 2000); one horse had a
previous history of laminitis (McCluskey & Kavenagh 2004) and one had severe systemic disease (Humber et
al 1991). A further three cases had evidence of severe systemic disease (Cohen & Carter 1992; Ryu et al 2004;
Winfield et al 2013). Of four iatrogenic laminitis cases reported amongst horses treated with dexamethasone
for pemphigus foliaceus, two non-surviving
cases for which serum albumin was measured were
hypoalbuminaemic (Vandenabeele et al 2004).
In conclusion, no studies that sought to investigate a potential causal association between
therapeutic
corticosteroid administration and laminitis were identified and there is currently insufficient evidence
to support such an association in healthy adult horses. There is weak evidence of an association
between administration of multiple doses of systemic corticosteroid and the onset of laminitis in adult
horses with underlying endocrine disorders or severe systemic disease. Therefore, underlying diseases
predisposing to laminitis should be considered prior to administration of corticosteroids, particularly
where multiple or large doses are indicated.
However, this knowledge summary has highlighted a paucity of
information on iatrogenic laminitis
and a well-designed cohort study is required to quantify the apparently
small risk of iatrogenic
laminitis following therapeutic administration of systemic corticosteroid.
Methodology Section
Search Strategy
Databases searched and dates
covered:
• PubMed accessed via the NCBI website (1950 – Present)
• Thomson Reuters Web of Science (1898 – Present)
• CAB Abstracts on the CAB Direct interface (1910 – Present)
• SciVerse Scopus (1823 – Present)
• International Veterinary Information Service (IVIS) database
(1997 – Present)
• Further relevant records were identified by the authors via
the bibliographies and reference lists of retrieved
publications and published conference proceedings.
Search terms:
(equine or horse* or pony or ponies ) AND (laminitis or laminitic)
AND (corticosteroid* or glucocorticoid* or dexamethasone or dex or
prednisolone or methylprednisolone or triamcinolone or TMC or
betamethasone)
Dates searches performed:
26/05/2015 and 27/05/2015
Veterinary Evidence
ISSN: 2396-9776
Vol 1, Issue 1
DOI:
http://dx.doi.org/10.18849/ve.v1i1.12.g19
next review date: 26 May 2017
page | 13
total pages: 17
Exclusion / Inclusion Criteria
No limitations regarding study design, setting, sample size or study population were imposed.
Exclusion:
N
on-English language, narrative or non-systematic review articles (or
non-systematic reviews published in conference proceedings or as
letters/correspondence), unpublished data, pharmacokinetic, in vitro
or in vivo experimental studies.
Inclusion:
Any reported case of laminitis occurring in an adult horse or pony
following the systemic administration of corticosteroid(s).
Search Outcome
Database
Number
of
results
Excluded –
non-
English
language
publication
Excluded – non-
systematic
review article,
conference
proceeding or
letter
Excluded –
pharmacokinetic
/ in vitro / in
vivo
experimental
study
Excluded – did
not answer
PICO question /
no iatrogenic
laminitis
case(s)
reported
Total
relevant
papers
NCBI
PubMed 34 1 10 6 13 4
Thomson
Reuters Web
of Science
84 1 31 12 34 6
CAB Direct 86 1 44 13 24 4
SciVerse
Scopus 66 5 30 7 19 5
International
Veterinary
Information
Service (IVIS)
database
70 0 69 0 1 0
Other
sources 7 0 1 0 1 5
Total relevant papers when duplicates removed 13
Veterinary Evidence
ISSN: 2396-9776
Vol 1, Issue 1
DOI:
http://dx.doi.org/10.18849/ve.v1i1.12.g19
next review date: 26 May 2017
page | 14
total pages: 17
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Veterinary Evidence
ISSN: 2396-9776
Vol 1, Issue 1
DOI:
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next review date: 26 May 2017
page | 15
total pages: 17
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Veterinary Evidence
ISSN: 2396-9776
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DOI:
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page | 16
total pages: 17
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Veterinary Evidence
ISSN: 2396-9776
Vol 1, Issue 1
DOI:
http://dx.doi.org/10.18849/ve.v1i1.12.g19
next review date: 26 May 2017
page | 17
total pages: 17
