Treatment of Pruritus

Allergen-specific Immunotherapy

Specific immunotherapy was introduced to veterinary medicine in the1960s. Since then several studies have been undertaken to evaluate the efficacy of allergy shots in dogs and cats. Despite the use of different allergens (aqueous versus aluminum-precipitated) and different protocols, the overall success rate was comparable and varied from 45% to 60% in studies with a follow-up of 1 year or longer to 70% to 100% in studies with a shorter duration.

In specific immunotherapy, an individual is exposed to extracts of antigens to which it has shown an allergic reaction. This exposure starts at low concentrations that are increased gradually over time and after reaching a maintenance dose, are either continued indefinitely or slowly tapered.

Considerations before Beginning Allergen-specific Immunotherapy

Clinically and relevant to daily practice, several key issues need to be discussed with owners before they consider allergen-specific immunotherapy or "allergy shots".

> The success rate: About 20% of the patients will do extremely well and thrive with no additional therapy; 40% of the patients do well, even though occasional additional treatments such as antihistamines, fatty acids and/or antibiotics are needed. Owners are happy with the improvement achieved and consider the allergy shots worthwhile, even though therapy may be lifelong. Another 20% of patients improve, but the degree of improvement is unsatisfactory. And in 20% of the patients, therapy has no influence on the disease process.

> The cost: This may vary depending on the country of practice, the dog’s allergies, the vaccines used, and the dose rates needed. Veterinary dermatologists are a good source of information for approximate expense.

> The time to improvement: First improvement may be seen as early as 4 weeks into therapy and as late as 12 months after starting the allergy shots. On average, improvement is expected after between 4 and 6 months.

> The duration of treatment: A minority of owners may discontinue their dogs' immunotherapy after 2 years, with their pets being permanently cured and symptom free. Other dogs, however, will require lifelong therapy!

> The involvement: Atopic dogs are "high maintenance" and as such need constant care, most likely at least initially regular rechecks and concurrent medication. Allergy shots are not an easy way out but at this point the best of many available treatments, all of which involve long-term administration of medications of some sort.

Points to Remember if you Have Patients on Immunotherapy

‡ Glucocorticoids may be given on an occasional basis at anti-inflammatory dosage levels without interfering with therapy.

> Antihistamines, fatty acids, and antimicrobials do not interfere with immunotherapy so that they may be, and often are, used concurrently.

♣ If the condition of patients receiving allergy shots suddenly deteriorates, always evaluate for infection. Yeast and bacteria are common complicating factors secondary to these allergies, which can cause dramatic increases in pruritus. Cytology will identify cocci, rods, yeasts and inflammatory cells and thereby guide antimicrobial therapy.

> If no infection is detected, antihistamines or glucocorticoids can be used to regulate the patient’s pruritus.

> If there is a regular increase in pruritus after the injection, the dose and frequency may need to be adjusted. Decreased doses may be helpful.

> If there is a regular increase in pruritus before the injection that is greatly improved by the injection of allergen extract, the time interval between the injections is probably too long and needs to be shortened. The dose may also be decreased in some of these patients without decreased efficacy.

> If there is no response to allergen-specific immunotherapy after 4 to 6 months, I recommend that you contact your nearest veterinary dermatologist for advice while there is still sufficient vaccine left to change the dose and frequency of the injections by adjusting them to the needs of that particular patient. Many patients need an approach suiting their particular requirements and the help of a veterinarian experienced in immunotherapy may be of great benefit.

I sincerely believe that allergen-specific immunotherapy is currently the best available treatment for canine atopic dermatitis, but it will only be successful in most atopic animals if owners and veterinarians have realistic expectations and are prepared to put in significant effort over the period that sometimes extends over many months. Only then will maximal benefit be achieved! In as much as the first months on immunotherapy may be draining for owner and veterinarian, consider offering referral to a veterinary dermatologist, particularly if you are not experienced in this therapy.

Antihistamines

> Antihistamines are useful adjunctive agents in the management of pruritic patients. The classical antihistamines act by blocking H1-receptors. First-generation antihistamines also have an anticholinergic, sedative, and local anaesthetic effect. Second-generation antihistamines penetrate less through the blood brain barrier or have a low affinity for the brain compared with the action on peripheral H1-receptors. Thus they are effective yet produce less sedation (Table 3-3).

> The advantage of antihistamines is the rare occurrence of adverse effects. Drowsiness is the most common finding and may decrease after 2 to 3 days of therapy. Thus, it may be worthwhile continuing treatment for several days before final evaluation. Less common are gastrointestinal signs. Acute poisoning following an overdose is characterized by CNS hyperexcitability. Due to the anticholinergic properties of terfenadine and cyproheptadine, these drugs should not be used in patients with severe cardiovascular disease, since they may cause hypertension.

> The necessity of frequent administration (two to three times daily) and the high cost of some antihistamines limit their long-term use in many patients, especially larger dogs.

> A further shortcoming in dogs is the relatively low success rate, which varies between 5% and 30%, depending on dosage and drug used.

♣ Cats are much more likely to respond to antihistamines than dogs. However, administering oral medication on a long-term basis may be challenging in this species.

> If a patient responds to antihistamine therapy and the owner is willing to maintain the animal on it, antihistamines represent safe long-term treatment that is preferable to glucocorticoids!

> Antihistamines in humans are not used to treat present symptoms but to prevent onset of symptoms. Thus, administration should not be intermittent assuming the same holds true in animals.

‡ The potential success rate can be increased by trying several different antihistamines sequentially because patients may be responsive to one antihistamine but not to another.

‡ Antihistamines have been reported to be effective in lowering the corticosteroid dose, even if they did not help the animal as a single therapeutic agent.

> Because the withdrawal time of antihistamines before an intradermal skin test is much shorter than that of glucocorticoids, they can be used to relieve pruritus during the preparation time where the latter are contraindicated.

Essential Fatty Acids

> Essential fatty acids (EFAs) are important for epidermal barrier function, as components of cell membranes, and as the precursors of inflammatory mediators.

> Supplementation with specific EFAs, especially linoleic acid (in sunflower and safflower oil), gamma-linolenic acid (in evening primrose oil) and eicosapentanoic acid (in cold water marine fish oil), can have anti-inflammatory effects. Linoleic acid is needed for maintenance of stratum corneum barrier function, limits transepidermal water loss and is thus better suited for the treatment of scaling (Table 3-4).

> Success rate of EFA therapy is relatively low in dogs, higher in cats.

> It may take several weeks of supplementation until clinical effects become evident.

> In essence, EFA supplementation decreases production of inflammatory prostaglandins and leukotrienes in favor of an increased production of noninflammatory or antiinflammatory prostaglandins and leukotrienes.

> Adjunctive therapy with essential fatty acids can be beneficial in a patient with allergies.

‡ Fatty acids have been reported to be effective in lowering the corticosteroid dose, even if they did not help the animal as a single therapeutic agent.

‡ Start with a small dose to avoid possible diarrhea and gradually increase the dose.

> Ideal doses and w-6/w-3 ratios are a subject of continuing active research.

Glucocorticoids

> Glucocorticoids are very commonly used in the treatment of skin conditions (Table 3-5).

> At anti-inflammatory dosage, they decrease inflammatory cell activity and migration.

> Corticosteroids are effective in most patients with atopic disease and resolve the symptoms at least initially on reasonably low dosages. Flea-allergic animals will also often respond to these drugs, although typically at slightly higher dosages.

> Glucocorticosteroids can be considered the treatment of choice in animals with a mild seasonal pruritus of 1 to 2 months duration that is controlled with anti-inflammatory dosages (<1 mg/kg) of prednisolone every other day.

> Every other day therapy is definitely preferred over daily drug administration because it is thought to lower the chances of iatrogenic hyperadrenocorticism.

> I use prednisolone at anti-inflammatory doses for severely affected dogs after skin testing and short term to break the itch-scratch cycle. However, the need to increase the dosage over time to control the clinical signs in most of these patients, combined with the potentially severe long-term side effects, make glucocorticoids a poor long-term choice for atopic patients.

> Adverse effects include polyuria, polydipsia, polyphagia, increased susceptibility to infection, and other well-known signs of iatrogenic hyperadrenocorticism. The most commonly encountered infections affect the urinary tract, skin, and lungs.

> Drugs should always be tapered to the lowest effective dose.

♣ Frequently, the dose necessary to control clinical signs can be decreased when adjunctive therapy is used. Fatty acids and antihistamines have been reported to be effective in lowering the corticosteroid dose, even if they did not help the animal as a single therapeutic agent. Regular topical therapy (e.g., shampoos) may be another means of decreasing the need for systemic glucocorticoids.

♣ I recommend to the owners of my atopic patients treated with glucocorticoids the lowest possible dose, on which the animal is mildly itchy but not uncomfortable. If no pruritus is present, the dose used is too high.

♣ The glucocorticoid dose needed in individual patients often varies seasonally.