Newest strides in treating acute laminitis (Proceedings)


Laminitis is frustrating for veterinarians because current knowledge and understanding of the pathophysiology and progression of the disease are incomplete, limiting efforts to prevent and treat this devastating disease successfully.

Laminitis is frustrating for veterinarians because current knowledge and understanding of the pathophysiology and progression of the disease are incomplete, limiting efforts to prevent and treat this devastating disease successfully. Scientific investigations have shed light on the pathophysiologic events involved with laminitis; however, additional studies are needed to unravel the remaining mysteries regarding the initiation and propagation of laminitis. Currently, numerous and varied therapies are used to prevent and treat laminitis; however, clinicians' preferences and impressions regarding the most effective treatments are based on an incomplete understanding of the initiating events in this disease. Because of the gaps in knowledge of the pathophysiology of laminitis, the effectiveness of the currently used treatments is inconsistent at best. In some cases in vogue therapies may actually be detrimental to laminar healing. Therefore developing a more thorough understanding of the cascade of events involved with the onset and propagation of acute laminitis should help veterinarians develop more rational, effective, and cost-efficient therapies.

Clinical Signs and Diagnosis

Laminitis is a disease that can affect all four feet; however, laminitis most commonly affects the forelimbs because they bear approximately 60% of the mass of the horse.3 The increased load of the forelimbs compared with the hindlimbs is thought to account for the increased occurrence of laminitis in the forelimbs. To define better the severity of clinical signs exhibited by horses, Obel established a grading system in 1948. Grade 1 is the least severe and states that the horse alternately and incessantly lifts the feet and that lameness is not evident at a walk but is evident at a trot as a short, stilted gait. Horses that walk with a stilted gait but still have a foot lifted are classified as grade 2. Horses with grade 3 laminitis move reluctantly and vigorously resist lifting of a foot. The most severe classification is grade 4, noted by the horse refusing to move unless forced.11 Other clinical signs characteristic of laminitis are heat present over the dorsal surface of the hoof wall, bounding of the digital pulse (increase in the difference between the systolic and diastolic digital arterial pressure), sensitivity to hoof testers, swelling of the coronary band, and alteration of stance to redistribute weight to the hindlimbs (sawhorse stance or rocking of weight to the hindlimbs) if laminitis is principally affecting the front limbs. More severe signs are a dropped sole or palpation of a depression located at the level of the coronary band, both indications of rotation or distal displacement (sinking) of the distal phalanx within the hoof wall.5,12 Lateral radiographs of the digit are indicated for detection of rotation and distal displacement of the distal phalanx within the hoof capsule.

Histopathologic Findings

Following the onset of lameness, the initial histologic alteration occurs in the digital vasculature, including swelling of the endothelial cells and mild edema formation.13 Laminar capillaries become obstructed with erythrocytes within 8 hours. Within 6 to 12 hours, a perivascular leukocyte infiltration occurs that then dissipates as the inflammatory cells migrate into the epidermal layer. Arteriolar endothelial cells become deformed because of cytoplasmic processes that extend into the lumen. Microvascular thrombi and accompanying severe edema formation occur within 24 hours, and hemorrhage occurs within the primary dermal laminae by 72 hours.

Primary histologic alterations of the laminae occur within 8 hours after lameness develops.13 Initially, thinning and lengthening of the lamellar structures is accompanied by reduction, flattening, and displacement of epithelial cells. The secondary laminae become redirected such that laminae nearer the base of the dermal lamina are directed toward the coffin bone and those nearer the laminar tips are directed toward the hoof wall. Morphologic alterations following epithelial cell damage include swelling, vacuolization, nuclear swelling and pyknosis, and leukocytic infiltration of the secondary epidermal lamina, which is observable as early as 24 hours after the onset of lameness.


Development of acute laminitis often follows other primary diseases; therefore the mechanisms involved in the pathogenesis of laminitis are most likely numerous and interrelated. Currently, inflammation, endothelial and vascular dysfunction, and metabolic disease are considered pivotal events in the development of laminitis.

Systemic sequelae to inflammation (systemic inflammatory response syndrome) commonly plague equine patients undergoing treatment for numerous conditions including pleuropneumonia, colitis, enteritis, peritonitis, endometritis, hepatitis, and neonatal sepsis. Although end organ damage from the systemic inflammatory response can include renal, hepatic, pulmonary, and cardiac disease and failure, there is no complication more common and devastating during equine inflammatory disease than acute laminitis. Although researchers once questioned whether the disease should be called "laminar degeneration" due to the minimal neutrophilic infiltration present histologically, application of more sensitive research tools has produced abundant evidence of inflammatory changes during laminitis. In laminitis, neutrophils become aggregated to platelets in the early prodromal stage and at the onset of lameness. Significant emigration of neutrophils and monocytes from the dermal capillaries occurs along with emigration of activated leukocytes from the systemic circulation which produce reactive oxygen species. Expression of interleukin-1 and interleukin-10 in dermal tissues is increased in horses with laminitis. Laminitis is accompanied by increased concentrations of meloperoxidase (MPO; a neutrophil enzyme) in plasma, laminar tissue, and skin providing convincing evidence for systemic activation of neutrophils, neutrophil emigration into the integument and laminae, and neutrophil degranulation. This active MPO released during neutrophil degranulation is capable of generating reactive oxygen species leading to lipid peroxidation of cellular membranes, most notably endothelial cells. Thus, local activity of MPO may reduce nitric oxide synthase activity leading to microvascular dysfunction during equine laminitis. Activated neutrophils also generate matrix metalloproteinase-9 capable of degrading the laminar basement membrane leading to laminar separation. Thus, evidence for the neutrophil's role in generating devastating tissue damage during equine inflammatory disease states is mounting.

There is also evidence for endothelial cell dysfunction during equine laminitis. Substantial increases in digital venous resistance facilitating laminar edema formation are early events in experimental laminitis. These vascular changes are accompanied by increased blood glucose, insulin, and platelet-neutrophil aggregates, and endothelin-1 suggesting endothelial dysfunction in equine laminitis. It was recently discovered that infusion of insulin for 48 to 72 hours leads to laminitis highlighting the importance of metabolic and endothelial events. Hyperinsulinemia alone can induce the inflammation and endothelial dysfunction observed in laminitic horses.

The sequel to the inflammation and endothelial dysfunction is activation of metalloproteinases. These are enzymes that are involved in the growth of the continually proliferating hoof wall past the distal phalanx. Laminin and type IV and type VII collagen are components of the laminar basement membrane. The enzymes metalloproteinase-2 and metalloproteinase-9 are believed to dissolve these substances, and under normal physiologic states, controlled dissolution allows the movement of epidermal laminae past the dermal laminae as growth occurs. Excessive activation of these enzymes leads to uncontrolled dissolution of the basement membrane components, resulting in separation of the epidermal laminae from the dermal laminae.

Based on these events prevention of laminitis should aim toward blunting the activation of neutrophils and ensuing inflammation, restoration of vascular and endothelial function, and abolishment of activation of the enzymes (MMPs) responsible for the dissolution of the basement membrane.


Treatment of laminitis remains empiric and often based on the experience and preference of the clinician. Effective treatment of laminitis requires aggressive and appropriate treatment of the primary disease process.

Recommended treatments include administration of mineral oil (if the horse engorged on grain) and intravenous fluids, parenteral antibiotics, nonsteroidal antiinflammatory drugs, and hyperimmune serum or plasma as appropriate to the primary disease process.

The first consideration in specific treatment of acute laminitis is to address the inflammatory process. Adequate safe medications are not available to this end. Nonsteroidal antiiflammatory drugs (flunixin meglumine, phenylbutazone) are indicated as cyclooxygenase activation in the laminae has been documented and analgesia is a needed benefit. However, the spectrum of inflammatory changes present in many cases exceeds the ability of these medications. Plasma contains naturally occurring anti-inflammatory proteins that produce a transient benefit; however the cost of plasma often precludes repeated administration. Corticosteroids are contraindicated as they have the potential to worsen insulin resistance and may cause laminitis. Fluid administration should be administered carefully to avoid worsening digital edema. Vasoactive drug therapy does not appear to be clinically efficacious.

Inflammation and enzymatic activation may be addressed via cryotherapy. This is a time- honored treatment; however, it is nearly impossible to achieve sufficiently low hoof temperatures with clinically available equipment.

Dimethyl sulfoxide (DMSO) is an antiinflammatory drug that scavenges hydroxyl radicals, decreases edema, and therefore is used to counteract the effects of ischemia-reperfusion injury. Although the involvement of ischemia-reperfusion and oxygen free radicals in the pathogenesis of laminitis is unclear, the fact that a biphasic decrease in laminar perfusion normalizes or increases during the intervening period suggests that hyperemia and subsequent ischemia-reperfusion injury may play a role. The reason DMSO has not been shown to be particularly effective in preventing or treating laminitis could be that ischemia-reperfusion injury does not occur or the dose or timing of DMSO is not appropriate. One should administer DMSO, if used, at a dose of 0.1 to 1.0 g/kg intravenously diluted in a polyionic fluid with dextrose to a concentration of 10% to 20% every 8 to 12 hours.

Drugs that reduce matrix metalloprotein enzyme activity are being administered by some clinicians to horses with or at risk of laminitis. Although hopes are that reduction of this enzyme activity will protect the laminae from insult, this has not been proven. There is evidence that MMP inhibitors commonly used in people are not effective in horses.

Efforts to reduce mechanical forces and stabilize the distal phalanx are imperative to effective treatment of acute laminitis. Horses should not be exercised during the acute stages because this can lead to increased mechanical forces that could lead to shearing of laminae. Owners should bed the stall deeply with sand or other material that provides support to the frog and provides some cushion if the horse spends long periods recumbent. Providing early and effective mechanical support of the distal phalanx can spare weakened, separating lamellae and improve the outcome. Ideally, one should institute mechanical support before or at the onset of foot pain. Frog support is one of the more effective methods of providing support to the distal phalanx and can be achieved by using roll gauze taped to the frog in the shape of a triangle. One also can use a commercially available triangular, rubber frog pad. Using a moldable material such as dental putty or a thermoplastic material, one can conform a frog support to the shape and sulci of the frog and sole, allowing for a more effective distribution of the mechanical support to the frog and subsequently the distal phalanx. One must take care to support the frog fully but not allow excessive pressure on the sole because this may increase pain.

Related Videos
© 2023 MJH Life Sciences

All rights reserved.