Frequency of equine laminitis: a systematic review with quality appraisal of published evidence

Equine laminitis is a highly debilitating disease of the foot. Despite its perceived importance, epidemiological characteristics are poorly understood and the true frequency of the disease remains unclear. The objective of this study was to retrospectively assess previous research to identify publications which provide the best evidence of the frequency of naturally-occurring equine laminitis. A systematic review of English language publications was conducted using MEDLINE (1950–2010), CAB Direct (1910–2010) and IVIS (1997–2010). Additional publications were included by searching bibliographies. Search terms included laminitis, equine, frequency, prevalence and incidence. Studies that allowed frequency estimations to be made for naturally-occurring equine laminitis were included. Information was extracted using predefined data fields, including 13 study quality indicators.Sixty-nine publications were appraised. Ten were considered to provide the most reliable information, estimating the frequency of equine laminitis ranging from 1.5% to 34%. Previous publications estimating laminitis frequency were generally poor quality. Laminitis frequency varied across publications however the publications included in this review focussed on many of the different underlying laminitis aetiologies and comparison of the frequencies between groups would be inappropriate. High-quality evidence-based studies are needed to estimate the true disease frequency in different equine populations.     

In vitro evidence for a bacterial pathogenesis of equine laminitis

Utilizing an in vitro laminitis explant model, we have investigated how bacterial broth cultures and purified bacterial proteases activate matrix metalloproteinases (MMPs) and alter structural integrity of cultured equine lamellar hoof explants. Four Gram-positive Streptococcus spp. and three Gram-negative bacteria all induced a dose-dependent activation of MMP-2 and MMP-9 and caused lamellar explants to separate. MMP activation was deemed to have occurred if a specific MMP inhibitor, batimastat, blocked MMP activity and prevented lamellar separation. Thermolysin and streptococcal pyrogenic exotoxin B (SpeB) both separated explants dose-dependently but only thermolysin was inhibitable by batimastat or induced MMP activation equivalent to that seen with bacterial broths. Additionally, thermolysin and broth MMP activation appeared to be cell dependent as MMP activation did not occur in isolation.These results suggest the rapid increase in streptococcal species in the caecum and colon observed in parallel with carbohydrate induced equine laminitis may directly cause laminitis via production of exotoxin(s) capable of activating resident MMPs within the lamellar structure. Once activated, these MMPs can degrade key components of the basement membrane (BM) hemidesmosome complex, ultimately separating the BM from the epidermal basal cells resulting in the characteristic laminitis histopathology of hoof lamellae. While many different causative agents have been evaluated in the past, the results of this study provide a unifying aetiological mechanism for the development of carbohydrate induced equine laminitis.     

A multicenter, matched case-control study of risk factors for equine laminitis

Risk factors for equine laminitis were examined in a prospective case-control study of the 258 cases seen at six collaborating veterinary teaching hospitals over a 32-month period. Case-control pairs were matched on institution, clinician, and season of diagnosis. The 90% of case-control pairs (78 acute, 155 chronic) that had complete data for age, gender, and breed were used in separate conditional logistic-regression models for acute and chronic laminitis. There was an increase in risk for horses with acute laminitis from 5 to 7 years of age (OR 4.7, 95% CI 1.3–16) and from 13 to 31 years of age (OR 3.9, 95% CI 1.3–12) (both compared to <5 years); risk was increased for chronic laminitis from 10 to 14 years (OR 3, 95% CI 1.4–6.8) and from 15 to 38 years (OR 2.9, 95% CI 1.4–6.1) (both compared to <6 years). Mares — but not stallions — were more likely than geldings to develop acute laminitis (OR 2.6, 95% CI 1.1–6.2) and chronic laminitis (OR 2.0, 95% CI 1.1–3.6). In the small acute-laminitis data set, the breed variable was collapsed into three categories: Thoroughbred (THB, reference), the Quarter Horse (QH), and other (non-QH-THB). The non-QH-THB group was at increased risk of acute laminitis (OR 3.8, 95% CI 1.2–11.8). For the seven breed-group categories used in the chronic-laminitis model, however, all non-THB breed groups appeared significantly at risk as compared to the THB, with odds ratios ranging from 3.3 (95% CI 1.3–8.30) for the QH to 9.1 (95% CI 2.1–39.3) for ponies.     

Bovine laminitis: clinical aspects, pathology and pathogenesis with reference to acute equine laminitis

This review deals with the features of clinical and subclinical laminitis in cattle. Prominent clinical signs of acute laminitis are a tender gait and arched back. The sole horn reveals red and yellowish discolourations within five days. In subacute and chronic cases clinical signs are less severe. In chronic laminitis the shape of the claws is altered. Laminitis is frequently followed by sole ulceration and white zone lesions. Blood tests showed no significant changes for laminitic animals. Arteriographic studies of claws affected by laminitis indicated that blood vessels had narrowed lumens. Gross pathology revealed congestion of the corium and rotation of the distal phalanx. Histopathologic studies indicate that laminitis is associated with changes of the vasculature. Peripartum management and nutrition are important factors in its aetiology. It is hypothesised that laminitis is evoked by disturbed digital circulation. In the pathogenesis of acute laminitis three factors are considered important: the occurrence of thrombosis, haemodynamic aspects of the corium, and endotoxins which trigger these pathologic events.     

The prevalence of endocrinopathic laminitis among horses presented for laminitis at a first-opinion/referral equine hospital

Endocrinopathic causes of laminitis may be a common underlying causative pathogenesis in first-opinion or field cases presenting with laminitis, as opposed to laminitis produced in inflammatory research models. This study aimed to determine whether evidence of an underlying endocrinopathy was present in horses presented for laminitis to a first-opinion/referral veterinary teaching hospital. A second aim was to compare the signalment of horses and ponies with laminitis with the equine hospital population during the same period. All horses presenting for laminitis at Helsinki University Equine Teaching Hospital, Finland, over a 16-month period were examined for an underlying endocrinopathy. Horses presenting for laminitis were compared with the hospitalized population over the same period. There were 36 horses presented for laminitis, and evidence of endocrinopathy was present in 89%. Of the horses showing an underlying endocrinopathy, one-third had a diagnosis of pituitary pars intermedia dysfunction, and two-thirds showed basal hyperinsulinemia indicative of insulin resistance, without evidence of hirsutism. Phenotypic indicators of obesity were present in 95% of horses with basal hyperinsulinemia without hirsutism. Compared with the hospital population during the same period, horses with laminitis associated with an underlying endocrinopathy were significantly older and more likely to be pony breeds. Our data support that endocrine testing should be performed on all cases of laminitis that do not have a clear inflammatory or gastrointestinal origin.     

Corticosteroid-potentiated vascular responses of the equine digit: a possible pharmacologic basis for laminitis.

Spirally cut digital arteries and veins were mounted isotonically in organ baths containing oxygenated Krebs' Q-Henseleit solution. Twelve arterial and 12 venous preparations all contracted dose dependently when epinephrine, norepinephrine, serotonin, or histamine were added to the bathing fluid. Addition of hydrocortisone or betamethasone alone did not cause contractions in any of the tissues tested. However, when hydrocortisone or betamethasone was added to vessel strips that were partially contracted (40% to 60% maximal) by epinephrine, norepinephrine, or serotonin, each vessel strip invariably underwent an additional contraction. In venous and arterial strips, dose-response curves to epinephrine, norepinephrine, serotonin, or histamine were established in the absence and in the presence of corticosteroid. Effects of the amines, except histamine, were markedly potentiated. The degree of corticosteroid/amine potentiation was greater for epinephrine than for norepinephrine and greater in the digital vein than in the corresponding artery from the same animal. Betamethasone was more potent than hydrocortisone.     

Cyclooxygenase expression in the early stages of equine laminitis: a cytologic study

BACKGROUND: Recent reports indicate increased amounts of mRNA from inflammation-related genes in the prodromal stage of laminitis. HYPOTHESIS: Cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) undergo distinct patterns of expression in equine laminae in the developmental stage (DEV) and acute clinical stage (LAM) of laminitis. ANIMALS: Horses selected from an outbred population were placed into 1 of 4 groups: DEV (n = 5), CON-3h (control group for DEV, n = 5), LAM (n = 5) and CON-10h (control group for LAM, n = 5). METHODS: Laminar and skin samples were obtained from (1) animals either undergoing leukopenia (DEV) or the onset of clinical signs of laminitis (LAM) after black walnut extract (BWE) administration and (2) animals either 3 (CON-3h) or 10 (CON-10h) hours after administration of water. Real-time quantitative polymerase chain reaction (RT-qPCR), immunoblotting, and immunohistochemical analysis were performed for COX-1 and COX-2. RESULTS: Upon immunohistochemical analysis of all 4 groups, COX-2 was expressed by most viable epithelial cells in both laminae and skin. COX-1 exhibited similar epithelial expression to COX-2 in skin epidermis, but was expressed exclusively in the basal layer of laminar epidermis. COX-1 protein was not detectable in dermal vasculature of equine skin or laminae, whereas COX-2 was present in endothelial and vascular smooth muscle cells of dermal vasculature in both skin and laminae in all groups. A marked increase in laminar COX-2 protein concentrations was detected on immunoblotting in the DEV group, although a lesser increase was observed in the LAM group. CONCLUSIONS AND CLINICAL IMPORTANCE: COX-2 protein expression is markedly increased in the resident laminar cell types in the developmental stage of BWE-induced laminitis.     

Risk factors for owner-reported occurrence of equine protozoal myeloencephalitis in the US equine population

BACKGROUND: Equine protozoal myeloencephalitis (EPM) is a serious and often fatal neurologic disease of horses, but few studies have investigated risk factors. OBJECTIVES: To evaluate operation- and individual-level factors associated with likelihood of the occurrence of EPM. ANIMALS: Data were collected as part of a study of the US equine industry from 1,178 operations representing 83.9% of horses and 51.6% of operations with > or =3 horses in 28 states. METHODS: Probability-based sampling was used to enroll representative operations in a cross-sectional study. Interviews were conducted to collect information regarding health and management of horses. A nested case-control study was used to investigate risk factors among individual horses. Interview data were combined with climate data, human population density, and opossum regional ecology categories. Data were analyzed using logistic regression to identify risk factors for the occurrence of EPM. RESULTS: Owners reported that 95% of EPM cases included in this study were diagnosed by veterinarians. Variables associated with EPM occurrence on premises included opossum regional ecology, reported exposure to small wildlife, climate, terrain, housing, choice of bedding material, method of storing feeds, equine stocking density, and primary use of horses. Among individual horses, age was most strongly associated with disease risk. Associations also were identified with sex, breed, primary use, and participation in competitions. CONCLUSIONS AND CLINICAL IMPORTANCE: Because the risk of EPM occurrence on operations is closely tied to factors that impact exposure to opossums, their feces, and their environment, controlling these exposures may be important in preventing the occurrence of EPM.     

The effect of a treatment protocol on the prognosis of equine laminitis

All horses and ponies with laminitis treated at the Department of Equine Sciences, Faculty of Veterinary Medicine, Utrecht University, between 1995 and 1998 were analysed retrospectively (n = 152). Based on the results of this study and on the world-wide knowledge on laminitis a standardised treatment protocol was adopted in 1999. Fifty-eight patients have been treated for laminitis between 1999 and 2001 following the treatment protocol. Compared to our hospital-population (orthopaedic patients), mares and ponies are at higher risk developing laminitis, but the prognosis does not differ between sexes as between breeds. Radiological evidence of rotation of the third phalanx seems to be of minor importance for the prognosis. Distal displacement of the third phalanx, however, seems to worsen the prognosis. The outcome of the acute cases is significantly better in the group treated following the protocol, than in the group without protocol. The outcome of the chronic cases is not influenced by the treatment protocol. Although the cases in both groups differ, as they are all clinical cases, our data suggest that the standardised treatment protocol results in a better outcome for cases of acute laminitis.     

Intracecal endotoxin and lactate during the onset of equine laminitis: a preliminary report.

Cecal fluid from two adult horses was assayed by the limulus amebocyte lysate system for endotoxin before and after carbohydrate overload of the gastrointestinal tract. There were increases in cecal fluid endotoxin concentrations at the 3-, 6-, and 12-hour samplings when compared with base-line values. Concomitant cecal fluid lactate concentrations and pH values increased and decreased, respectively. Both horses subsequently developed clinical signs of acute laminitis.     

Evaluation of low-molecular-weight heparin for the prevention of equine laminitis after colic surgery

Objectives – The aim of this study is to describe the prevalence of postoperative laminitis in colic cases and to determine if low-molecular-weight heparin (LMWH) is effective in preventing this complication.
Design – Retrospective clinical study.
Animals – Client-owned horses.
Interventions – SC administration of enoxaparin during the postoperative period.
Measurements and Main Results – Medical records of 360 horses undergoing surgery for colic and surviving at least 3 days were evaluated. Fifty-six horses admitted before 1995 did not receive LMWH (control group) and 304 admitted after 1995 received LMWH as a prophylaxis for laminitis (treatment group). Three grades of severity were defined for laminitis. Prevalence and severity of laminitis were compared between the 2 groups. Several parameters recorded on admission (sex, age, breed, site and nature of the disease, heart rate, PCV, gravity score, and shock score) and the administration of LMWH were tested as risk factors in the development of laminitis in a logistic regression procedure. Prevalence and grade of laminitis were significantly lower in the treatment group. Only the absence of LMWH was recognized as a significant risk factor in the logistic regression model.
Conclusions – The administration of LMWH appears to be effective in the prophylaxis of laminitis following colic surgery and may be useful in the postoperative management of these horses.     

Risk factors for equine acute abdominal disease (colic): Results from a multi-center case-control study

Many causal hypotheses for acute equine abdominal disease (colic) have been proposed. However, few epidemiologic studies have been undertaken to identify risk factors for the syndrome. Risk factors for equine colic were identified using a hospital-based, multi-center, case-control study. Horses admitted with abdominal pain to Cornell, Guelph, Ohio State, Pennsylvania or Tufts university veterinary hospitals between March and December 1991 were selected. Control horses were randomly selected from a list of all other non-colic admissions. The person(s) responsible for the day-to-day care of the horse completed a telephone questionnaire. Risk factors were identified using multivariable logistic regression analysis.

A total of 406 colic and 406 control horses were used in the final analysis. Age, breed, outdoor access (pasture or drylot), outdoor water supply, use of a daily worming product, amount of concentrates and whole-grain corn consumed, type of person responsible for the day-to-day care of the horse and previous colic history were all significantly associated with colic risk. Arabian horses were more than twice as likely to be colic cases (OR = 2.0, 95% CI = 1.0–3.9), whereas Standardbred horses were nearly half as likely (OR = 0.6, 95% CI = 0.4–1.0) to be colic cases compared with the comparison Thoroughbred group. Horses that had access to outdoor enclosures without a continuous supply of water were more than twice as likely (OR = 2.2, 95% CI = 1.2–4.3) to be colic cases compared with horses that had an adequate supply of water on outside enclosures. The use of a daily worming product for at least 60 days during the 12-month period prior to presentation was associated with a significantly lower colic risk (OR = 0.11, 95% CI = 0.02–0.55). Colic risk increased with greater consumption of whole-grain corn; however, when all non-roughage concentrate feeds were combined, colic risk decreased with increased intake of concentrates. Significant interactions were identified between age and drylot use and between the type of care-person responsible for the day-to-day care of the horse (owner or non-owner) and previous colic history.

The findings of this study illustrate the complex multi-factorial nature of equine colic and point towards the importance of the overall quality of stable management and care, as well as the type of outdoor enclosure (pasture or drylot), water access, carbohydrate intake, parasite control and intrinsic (breed-related) factors.