Immune-Mediated Diseases in Dogs and Cats: When Are Steroids Not Enough?

By Andrew Woolcock, DVM, DACVIM (SAIM)│ 2023 Pacific Veterinary Conference Speaker

Immune-mediated diseases pose diagnostic and therapeutic challenges for small animal veterinarians. There are many inciting factors, be they disease-related or environmental, which can act as triggers to the immune system and lead to an exaggerated or deleterious response and subsequent immunemediated disease. Diagnostically, it can be very difficult to identify these triggers, and therefore these diseases are most often determined to be idiopathic in origin.

Without a clear cause, the choice of treatment for these diseases can be unclear. While it is accepted that most patients will benefit from pharmacologic suppression of the immune system, there is no consensus about the best regimen to achieve this suppression. Additionally, without identifying an underlying cause, it can be difficult to have confidence that immune suppression should be the sole mechanistic approach to treatment, making the monitoring of patients on therapy that much more important.

Prednisone, and other systemic corticosteroids, have long been the gold standard of treatment for immune-mediated diseases in dogs and cats. In addition to the ease of accessibility and low cost, corticosteroids have a broad mechanism for immune suppression, including inhibitory effects on aspects of the innate and adaptive immune system. Corticosteroids reduce the function of neutrophils and complements, while also causing apoptosis and decreased proliferation of lymphocytes. In addition to these broad effects, corticosteroids have a rapid onset of action. When used at appropriate doses, corticosteroids can be suppressive to these immune responses within about 3-5 days. For these reasons, corticosteroids will likely remain the gold standard for immune suppression in dogs and cats, especially for severe immunemediated diseases for which rapid therapeutic effect is necessary, like immune-mediated hemolytic anemia (IMHA), immune-mediated thrombocytopenia (ITP), and systemic lupus erythematosus (SLE).

Prednisone and other corticosteroids are catabolic in nature. Over time, these effects can lead to a number of adverse effects. In addition to the expected polyuria, polydipsia, polyphagia, and panting, long-term use of high-dose corticosteroids can lead to significant dermatologic issues like alopecia, thin skin, and calcinosis cutis. Corticosteroids also lead to muscle atrophy and ligament/tendon laxity, which can lead to musculoskeletal issues like weakness and injury. These effects on muscle mass and mobility can be especially severe in large and giant breed dogs, who tend to have a lower tolerance for high-dose corticosteroids when compared to smaller breed dogs and cats.

Adjunctive immune-suppressive agents have been used for decades, but the indication for their use, the choice of drug, and the approach to concomitant corticosteroid therapy have no clear guidelines. The most common adjunctive immune-suppressive agents used presently include azathioprine, cyclosporine, leflunomide, and mycophenolate. These medications each have their own unique mechanism of action but, in general, their effects are primarily on lymphocytes and the adaptive immune response. While their utility in veterinary medicine has been documented for years, the logistics of their use including optimal dosage, expected side effects, time to onset of immune suppression, and therapeutic drug monitoring are still active areas of discovery.

In general, the use of these drugs should be guided by patient factors including size and expected side effects, and disease factors including severity and response to corticosteroids. Patients with a lifethreatening disease like IMHA, or who have not demonstrated a response to corticosteroids within the first week or so of treatment, might require a more aggressive therapeutic regimen, including an adjunctive immunesuppressive agent. Other patients may respond readily to corticosteroids, but due to size or sensitivity to steroid side effects, they may benefit from an adjunctive immune-suppressive medication in order to allow a more rapid tapering of steroids and ameliorate adverse effects.

Developing an understanding of these immune-suppressive medications and the clinical scenarios for which more than one medication is indicated can help clinicians achieve more rewarding outcomes in these challenging cases.

The focus of Dr. Woolcock’s presentations at the 2023 Pacific Veterinary Conference will be on immune-mediated diseases in dogs and cats, as well as on common immune-suppressive medications and their use.

Andrew Woolcock, DVM, DACVIM, is an associate professor of small animal internal medicine at Purdue University. His interests include immune-mediated diseases, endocrinology, and the scholarship of teaching and learning. He has published several articles and book chapters, given lectures throughout the United States and internationally, and has received several awards for teaching and mentorship in the profession. His research program investigates the role of oxidative stress in inflammatory disease states of the dog and cat.