Laminitis has been around for millions of years. However, only in the last century (and primarily over the past 25 years) have we dramatically expanded our understanding of the pathophysiology, potential treatment protocols and prevention methods for this equine disease. Our ability to treat and prevent laminitis is still in its infancy, compared with the millions of years it has been afflicting horses.
We now understand that there are four main forms of laminitis: endocrinopathic, sepsis-induced or systemic inflammatory response syndrome (SIRS)-associated laminitis, support- or contralateral-limb laminitis and traumatic laminitis.
In endocrinopathic laminitis, hyperinsulinemia and elevated ACTH concentrations (Cushing’s disease) are the main triggers. Risk factors include obese horses, those with pituitary pars intermedia dysfunction and those with equine metabolic syndrome (EMS).
Endotoxemia or sepsis may cause sepsis-induced laminitis, which involves increased levels of inflammatory mediators (cytokines) such as chemokines and tissue necrosis factor (TNF), among others. Matrix metalloproteinases can become up-regulated with the inflammatory cascade and play a role in the breakdown of the basement membrane and separation of the epidermal and dermal lamellar tissue.
Support limb laminitis may be a result of altered blood flow in the foot because of a decrease of loading and unloading. Glucose metabolism may also be affected during overloading of the support limb, which can contribute to lamellar damage.
Each form of laminitis has its own unique triggers, but at some point in the disease progression, the results are the same—an inflamed and damaged lamina (see “Anatomy of laminitis” on page E8). In recent years, we’ve acquired a better understanding of disease progression. Laminitis is divided into four phases: developmental, acute, subacute and chronic.
Developmental phase. This phase is the period between the initial incident or exposure to the causative agent up to the onset of clinical signs (which may include lameness, increase in digital pulses with or without fever). It generally lasts 24 to 60 hours.
Acute phase. This phase is defined by the onset of clinical signs, including bounding digital pulses, lameness, heat and possible response to hoof testing. If the horse doesn’t experience mechanical failure of the foot, the acute phase is over within 72 hours of the onset of clinical signs and is followed by the subacute or chronic phase.
Subacute phase. This phase occurs if there is minimal damage to the lamellae and no radiographic evidence of rotation or sinking of the third phalanx (P3). This is an important time to prevent disease recurrence and to heal the foot. Clinical signs that were seen in the acute phase will resolve in the subacute phase, and the horse will become sound with healing. This phase can last up to several months.
Chronic phase. This phase is initiated if lamellar damage is not controlled and rotation or distal displacement (sinking) of P3 occurs. Chronic laminitis can cause coffin bone remodeling and decreased sole concavity (dropped sole). Development of a lamellar wedge (in other words, disorganized hypertrophied lamella or “scar horn”) can also result. This will cause an improper interdigitation of the lamellae between the coffin bone and hoof capsule. There can also be damage to the solar dermis, preventing growth.
Prevention and treatment
Despite our new and better understanding of laminitis pathophysiology, treatment continues to pose a challenge. Ideally, veterinarians would be able to identify horses at risk for developing laminitis and better manage them through diet, exercise and medications (for example, pergolide for Cushing’s disease, metformin for EMS) so they never get to the developmental stage of laminitis, says James Orsini, DVM, DACVS, associate professor of surgery and director of the Laminitis Institute at the University of Pennsylvania’s New Bolton Center.
Orsini and researchers at the New Bolton Center are looking at improved ways to identify the at-risk horse, using epidemiology studies before the developmental phase sets in and biomarkers during the developmental phase. Their goal is to develop a stall-side test.
Once a horse develops laminitis, there are several newer treatment modalities to address the pain and aid in healing.
Cryotherapy. For horses with sepsis or SIRS, initiating cryotherapy at the start of the illness can be beneficial. How and when the veterinarian institutes cryotherapy is critical to its success. At the University of Pennsylvania, Orsini and Andrew Van Eps, BVSc, PhD, MACVSc, DACVIM, studied the best methods for adequately cooling the feet of at-risk horses. It’s generally accepted that cold therapy should be continuous for 48 to 72 hours, during the entire developmental phase and for another 24 hours beyond the end of clinical signs of the primary disease. It’s important to include the foot, pastern, fetlock and distal cannon region in the cold therapy for the best results and to maintain intimate cold contact with the limb to achieve therapeutic temperature ranges.
The suggested range for therapy is from 41 to 50 F (5 to 10 C). To achieve intimate contact, crushed ice is preferable to ice cubes. Ice wraps were not suitable because of their size and the air space created between the wrap and the leg. Dry cold therapy provided by a Game Ready Equine system (CoolSystems Inc.) provided the most intimate contact and also provided intermittent pressure that may aid in blood and lymphatic flow. Treatment should continue 24 hours beyond resolution of the primary disease. New studies are demonstrating the benefit of cryotherapy in the early acute phase.
Pain management. Pain management has improved despite the fact that phenylbutazone and flunixin meglumine are still the primary NSAIDS in use. Orsini says that the administration of newer cyclooxygenase-2 (COX-2) inhibitors, such as firocoxib (Equioxx—Merial), make better sense and seem particularly useful in many of the chronic laminitis cases.
Mechanical support. Methods for mechanical support have improved in recent years, and all are designed to relieve forces on the laminar tissue, unload the sole corium (especially at the toe) and move the break-over back to improve comfort and stimulate sole growth. These include roller shoes, synthetic shock-absorbing shoes that reduce vibration and glue-on shoes. Pour-in pad products or dental impression material can also provide sole support. Soft-Ride (Soft-Rider Inc.) boots are another option.
To provide mechanical support and stability that allow the foot to grow, Scott Morrison, DVM, of Rood and Riddle Equine Hospital in Lexington, Kentucky, says that using a deep digital flexor tendon (DDFT) tenotomy combined with derotational shoeing can help many cases. “A normal horse is a toe loader. With rotation of P3, you get pressure on the sole corium that prevents it from growing,” says Morrison. “If you cut the DDFT, you move the load back. Once you shoe the foot to get the coffin bone parallel to the ground, you have relieved the pressure, and the sole corium will grow.”
Bisphosphonates. Both Orsini and Morrison agree that bone disease of P3 is occurring earlier in the disease process than once thought and before it is radiographically apparent. Inflammation of P3 leads to bone loss. Data are still lacking, but science suggests that bisphosphonate drugs such as Tildren (Ceva) and Osphos (Dechra) may be beneficial. By decreasing ostoeclastic activity, the drugs can help stop bone pain, damage and loss.
Stem cell therapy. Also promising, stem cells are thought to help in the repair phase after rotation, and Morrison thinks they can influence healing in the lamellar zone. Treatment is via regional limb perfusion. As the lamellae begin to heal, the process often occurs in an unorganized and a hypertrophied manner. This can result in a lamellar wedge—a thick, rubbery unstable mass of tissue that prevents proper attachment of the coffin bone to the hoof capsule.
The critical period of lamellar wedge formation appears to be 60 days after rotation, so the critical period for stem cell therapy would be before the 60-day mark. Once the lamellar wedge forms, stem cell therapy does not appear to change or improve this tissue. “Cases that are treated with stem cells early after rotation radiographically heal back tighter,” Morrison says. Stem cells are an exciting adjunctive therapy, but differentiation of stem cells would be an improvement, he adds. A cell that is more specific and effective for laminar tissue could improve outcomes.
When it comes to laminitis therapies, progress is slow, says Orsini. Future research will include exploring better ways to deliver matrix metalloproteinase inhibitors more cost effectively as a potential treatment for sepsis-induced laminitis, as well as exploring the role of stem cells and other regenerative therapies.