Abstract: This paper describes the aspects of the management of canine atopic dermatitis: treatment of complications, specific therapy (allergen eviction, immunotherapy) and symptomatic therapy.
Treatment of dermatoses which are related or secondary to atopic dermatitis
1. Treatment of microbial infections
An adequate antibacterial treatment regimen of secondary pyoderma, based upon systemic antibiotics and appropriate antibacterial topicals, may return the animal to a quasi-normal state. Such a case of CAD will only be treated in cases of regular reoccurrence of pyoderma and/or if the clinical signs of CAD itself become a concern. Also, some atopic dogs will respond to a well carried out antibiotic treatment, even without visible signs of secondary pyoderma. A true bacterial overgrowth (BOG) syndrome is plausible in such cases and the author treats with antibiotics patients showing an abundant cocoid surface flora after cytological tests, as an empiric therapeutic test.
The same reasoning is undoubtedly applicable as well to cases of Malassezia dermatitis. Systemic (ketoconazole) and topical therapy are required with a careful follow-up.
2. Treatment of FAD
A well conducted flea control regimen can eliminate the FAD and therefore, in certain cases can enable the animal to fall under its pruritic threshold. In such a case, atopic dermatitis treatment is not necessary if the clinical signs are not obvious. If this not the case, the atopic dermatitis should be treated while maintaining absolute antiparasitic treatment.
3. Management of food reactions
As discussed above, food intolerance may resemble CAD and a food elimination diet and the eviction of an offending food are relatively easy to perform.
4. Treatment of keratoseborrhoeic skin disease
A keratoseborrhoeic disorder can occur in CAD particularly in ancient cases. Treatment is mainly topical although systemic Essential Fatty Acids, used in the treatment of CAD may have an effect on seborrhoea. Shampoos and moisturizing agents are valuable supporting therapy in keratoseborrhoeic skin disorders.
5. Treatment of otitis externa
Otitis externa is a major feature of canine atopic dermatitis which causes inflammation of the external ear canal and ear pinnae. Secondary infections occur (bacterial and fungal) and perpetuating factors such as hyperplasia of epidermis and both sebaceous and apocrine glands lead to chronicity. It is typically erythemato-ceruminous at the beginning of the disease and it becomes eventually suppurative. The associated lesions of the ear pinnae (lichenification, alopecia, crusting) require therapy. Ear cleansing must be repeated regularly (e.g., twice or three times a week). Numerous commercial otic preparations are available which are usually easy to use and effective. They contain active substances such as antibiotic, antifungal and corticosteroid agents. Selection must be made after performing a smear and bacterial culture and sensitivity testing if the smear shows rods and/or if the otitis is suppurative. Corticosteroids included in otic preparations reduce pruritus, pain and proliferative reactions. They also decrease cerumen secretion. Systemic antibiotic therapy is often useful in otitis externa due to CAD, particularly if it is suppurative, because of associated otitis media. Surgical therapy can be avoided in many circumstances with appropriate medical therapy. Surgical failure is often due to failure to recognise and control CAD.
6. Treatment of pyotraumatic dermatitis
Lesions of pyotraumatic dermatitis are common in CAD. They are poorly understood. They should be differentiated from pyotraumatic folliculitis. Although there may be a spontaneous healing in a few days, treatment is beneficial. Clipping and cleansing with antiseptic shampoos can be followed by the application of creams containing antibiotics and corticosteroids. If pruritus or above all pain are important, a short systemic glucocorticoid treatment is useful.
1. Allergenic eviction
Allergenic eviction is "theoretically" the ideal treatment for all cases of allergic dermatitis. Totally avoiding the allergen may enable the animal to fall beneath its pruritic threshold, identical in this instance to the allergic threshold. This avoidance is illusive in the case of pollens. However, it is possible to eliminate environmental feathers and fabrics, and moulds can be destroyed by antiseptic or antifungal sprays or even anti-mould paint. However, the role of these allergens in dogs' atopic dermatitis is minimal and moreover feathers and fabrics are mostly sources of house dust mite allergen.
Various methods exist to fight against house dust mites and these may be tried around atopic dogs: elimination of furnishing fabrics, carpets, curtains, cushions etc, frequent vacuuming with a High Efficiency Particle Air filter vacuum cleaner which will not leave mites' particles suspended in the air, use of air dehydration and purification devices, use of acaricide sprays and foggers (some of which contain an Insect Growth Regulator [IGR] and a denaturing agent such as tannic acid which is very efficient for both mites' faeces and fungal spores), use of anti-mite mural paints (also anti-insect and anti-mould), use of cushions and covers which can be washed at high temperatures as beds for dogs, and use of protection covers produced for asthmatics if necessary (e.g., made of teflon, though these are expensive). The elimination of house dust mites may be effective in human atopic dermatitis but only one preliminary study has been published in canine dermatology.
2. Allergen specific immunotherapy
Specific immunotherapy (hyposensitisation, desensitisation) has been used in humans, since the beginning of the 20th century, to treat asthma and allergic rhinitis but never in dermatology (it is also used in cases of hypersensitivity to hymenoptera bites). It first was reported in dogs in the 40s, expanded in North America in the 60s and in Europe in the 1980s. The first explanation for desensitisation efficacy in man was in the production of blocking antibodies (lgG), which combine with allergens before they combine with the IgE. Today, many mechanisms are proposed. In brief, the intervention of other anti IgE anti-bodies (IgG anti IgE, anti-idiotype anti-bodies) has been proposed as well as allergen-specific IgG immune complex which regulate the immune response. In the same way, acting on Th2-Th1 substitution will lead to a reduction in the IL4 production and an increase in the INF-gamma production. The IL4 offers potential for the IgE synthesis, increases the number of weak affinity IgE receptors or their CD23 soluble form. The INF-gamma inhibits IgE synthesis. Late phase reaction inhibition in desensitized subjects is accompanied by the apparition of T-lymphocytes with a Th1 profile. Finally, desensitization may be accompanied by a cellular and tissue hyposensitisation by reducing the basophilic reactivity, blocking the eosinophilic migration, reducing the neutrophils' chemotactic activity and abolishing the cytotoxic activity of platelets, among others. These mechanisms can sequentially intervene and differ between the induction and maintenance phases. Halliwell reports IgG and IgE variations in dogs, in both directions, over a 2 year period without any clinical correlation. It is reasonable to think that the blocking anti-bodies' hypothesis is only a simplification and that no single mechanism can explain the dog's immunotherapy efficacy.
The choice of allergens mainly depends on the in vivo or in vitro test results. Skin tests represent the reference to identify the responsible allergens if they are correctly carried out. The use of biologically standardised allergens, even using human allergy techniques, is preferred. The ELISA techniques' serological diagnosis is attractive due to its simplicity (specific IgE assay). Specificity is usually low, there is a controversy about the reproducibility and sensitivity can be so high that positive predictive value is very low, which renders the test void. The polyclonal antibodies can have superior values but if many monoclonal anti-bodies are used grouped, good results can be achieved. Recently an innovative technique using human specific IgE receptors (FcεR1α) has been proposed. Test results are to be interpreted in an anamnesis and clinical light in each of the cases. Therefore, it must be logical to include allergens in a desensitization protocol (in the case of a positive reaction, danders, moulds, pollens, etc., are only used if they are present in the environment). This principle must however be nuanced in the case of cat's dander.
No standardisation exists for the methods used. Only aqueous extracts are used in North America, whereas in Europe, mainly alum precipitated extracts are available. It seems that the combination of moulds and pollen extracts alters their quality (due to the presence of protease in the mould extracts) and that different types of vials are necessary. Immunotherapy is efficient in man as testified in the results obtained in allergic rhinitis. The results are more or less difficult to evaluate in dogs. In fact, they depend on the animals (age and especially diagnostic criteria), evaluation criteria (telephone follow-up, clinical score), follow-up duration, and recognition or not of "loss of follow-up" as setbacks.
Presently, it is considered that 50 to 80 % of animals respond to immunotherapy in open studies. T. Willemse demonstrated in 1984 the method's efficacy through a double blind placebo controlled study. The 9-month evaluation seems important: it is usual that improvement at this stage is followed by success. The result variation factors are (apart from the diagnostic value and the clinical criteria of each one) the allergen identification method, specificity, allergens nature (Dermatophagoides spp), number of allergens, breed, age and patients' follow-up. The use of highly purified allergens (Der f 15 and Der f 18?) could improve results. No study has yet proven that the use of corticosteroids during desensitisation would have a very harmful effect on its efficacy.
Rare cases of secondary effects have been mentioned in an anecdotal manner (urticaria, angioedema, anaphylaxis). An exacerbation of clinical signs' is often noticed in the hours following injections. Limited local reactions which are spontaneously reversible often appear with alum precipitated extracts. A majority of veterinary dermatologists believe that the efficacy and absence of secondary effects justifies ad vitam eternam hyposensitization. They empirically remarked that the clinical signs reappear in a period of months to years after the treatment has been stopped.
Rush immunotherapy could be effective but secondary effects occur in a fourth of the cases.
This is useful at the beginning of immunotherapy (within the first year in successful cases) or on a long-term basis in failed cases (total or partial), or even in cases where immunotherapy is not required (aged animal, owner's hesitation or even, clinically slightly worrying cases apart from a few signs).
Corticosteroids are the most effective medications amongst the symptomatic treatment of allergic dermatitis. They have a powerful anti-inflammatory and anti-pruritic activity. They act at almost all inflammation and immunologic response stages. Their activity, however, varies tremendously. There is no consistency in the individual reaction not only in relation to the corticosteroid used but also for the same corticosteroid. The effect is reduced over time, and the doses required are increased. They are used topically or systemically. Topical application is of limited value because of the hair but could be useful in some cases (shampoos, sprays...). Systemic therapy should be limited to the oral administration of prednisolone or methyl-prednisolone (0.5 to 1 mg/kg/day during 5 to 7 days followed by 1 mg/kg every other day, as shortly as possible). Systemic corticosteroids have significant side effects and the following rules must be respected regarding the long term side effects of corticosteroids: use them as little as possible, use the lowest dose possible, preferably every other day and only if alternative anti-pruritic medications have been deemed inefficient.
2. Non steroidal topicals
Various non steroidal topicals can be used. Due to the probable skin penetration of allergens, the mechanical allergenic eviction effect of shampoos is likely to be beneficial. Anti-seborrhoeic shampoos and humectant sprays may be used to treat xerosis. Some of these contain oatmeal colloidal extracts with an antipruritic action. Recently a shampoo containing linoleic acid (reinforcing the lipid barrier), mono-oligosaccharides and vitamin E (immunomodulatory effects) and piroctone olamine (antiseptic) has been available. Some local use sprays (e g containing menthol and hamamelis extracts) may soothe erythematous and excoriated areas. A lotion containing mono-oligo saccharides, vitamin E, linoleic acid and chitosanide has been put on the market in conjunction with the aforementioned shampoo. Rinses containing pramoxin, a local anaesthetic, could also be helpful.
Some antihistamines, which block H1 receptors may be useful (antiH2 are inefficient). Many studies have been performed but there is insufficient evidence to conclude for or against the efficacy of antihistamines for treatment of CAD. Perhaps the most efficient products are clemastine, chlorpheniramine, hydroxyzine, oxatomide and diphenhydramine with approximately 20 to 30 % good results. However, only one placebo controlled double-blind study has been carried out, using astemizole, clemastine and trimeprazine. Moreover, some frequently used products such as cetirizine or ketotifen have not been evaluated at all. Oxatomide also blocks intracellular calcium transport with ketotifen and rupatidine equally blocking other mediators. The relatively low success rates of these antiH1 justify successive tests during at least one week at a time, until a satisfactory result is obtained. Trimeprazine, which alone is inefficient, has proven to be able to clearly reduce the need for prednisone. There is a synergic effect between the essential fatty acids and antihistamines.
4. Essential fatty acids
Essential fatty acids (EFA) have been the subject of many clinical studies. The fatty acids that have been studied are polyunsaturated, administered by oral route, especially omega-3 series eicosapentanoic acid (EPA) and omega-6 series gamma linolenic acid (GLA). These fatty acids compete with the arachidonic acid in the cascade of eicosanoids synthesis where leukotrienes and prostaglandins are formed having an anti-inflammatory activity or at least a pro-inflammatory activity which is much less significant than that observed with the metabolites emitted from arachidonic acid. Doses are variable and empirical. Height double blind placebo controlled studies have been done, including three in cross-over and results are variable. However, various elements have not yet been made clear: dosage (varying from 2 to 10 times the advised doses), optimal ratio between omega-3 and omega-6 (between 5 and 10), the minimal duration of the therapeutic test to predict efficacy (1 to 12 weeks), the function of co-factors, the usual diet and its essential fatty acid content as well as associated therapeutics. The reaction of atopic dogs to fatty acids varies and in practice, they are to be principally used with other anti-pruritic treatments. A dietary approach, based on the quantity of omega-3 and the ratio omega-3/omega-6 may also be helpful.
5. Non-steroidal anti-inflammatory agents
Anti-depressors: Fluoxetine, an anti-depressive agent which inhibits serotonin uptake and amitriptyline, a tricyclic anti-depressive agent with a antiH1 activity, appears to be moderately efficient giving good results comparable to the "best" antihistamines (20 to 30 %).
Leukotriene inhibitors have been tried in a few clinical trials. Zileuton, for instance, was not very effective in a placebo controlled study.
Misoprostol, a prostaglandin E analog, has shown interesting effects, including within a blinded placebo controlled study.
Phosphodiesterase inhibitors have shown a moderate efficacy in comparative (arophylline) or double blind placebo controlled cross-over (pentoxifylline) studies.
Immunomodulating macrolides: Cyclosporine (orally administered) is an effective drug for the treatment of CAD, as in man. This has been shown in a double-blind placebo controlled study. Furthermore no significant difference was found in recent comparative studies vs prednisolone or methylprednisolone.
Various agents, capsaicin, an injectable formulation of fatty acid copolymers, a phytotherapy preparation of Chinese herbs.
Conclusion: combination therapy case management
Each case is different and deserves a "combination therapy", which associates treatment of complications, eventual allergen eviction measures, allergen-specific immunotherapy and symptomatic therapy. It is the key to success.
References are available upon request.