Dermatitis Atopica Canina - (Manejo de las Recidivas)
The purpose is to emphasize on the chronic condition of CAD, in order to prevent and control early recurrences, avoiding the establishment of the most common complicating agents.
Pruritus as an early sign, clinical denominator and self-trauma complicating generator in atopic patients, is caused and also perpetrated by the presence of infectious agents: Yeasts and bacteria, microorganisms that participate in the crisis, as causes for initiation, increase and sometimes triggers of exacerbation episodes in previously controlled patients. Demodex mites' coexistence must also be confirmed or ruled out, since many patients are affected by the emergence of co-infections caused by pyodemodicosis (Piodemodexia) and malasseziasis (levurosis).
The patient affected by CAD, that was correctly controlled but, after clinical remission of pruritus had been achieved with conventional therapy, symptomatic exacerbation occurs so we should inquire about the coexistence of various crisis-triggering factors, such as parasitic infections, metabolic disorders, systemic infections, malassezial hyperproliferation, bacterial overgrowth or Demodex (one, two or all three diseases) must also be considered and properly identified for proper treatment.
If prednisone shows to be effective for the control of inflammation and pruritus, call on the use of prednisolone or methylprednisolone, and when the dose of cyclosporine is inefficient, increase the dose per kg.
When the response to steroid therapy and/or cyclosporine is ineffective, or pruritus has been definitively refractory and additional causes of failure in therapy (infectious and/or parasitic) have been properly evaluated and none of them can be identified, two diagnostic alternatives are left: a) It is a case of therapy refractory pruritus with steroids and/or cyclosporine, as it is proven that not 100% of patients with CAD are yet responsive to this bimodal therapy, or b) Consider misdiagnosis. Also today, pruritus control can be achieved by JAK inhibitor therapy (Janus kinase) on IL-31: oclacitinib.
When clinical signs and histopathological findings continue to support a CAD or atopic-like dermatitis, a more aggressive immunosuppressive therapy is mandatory to control inflammation and pruritus for these few, but existing refractory cases.
Skin, as the largest and most extensive organ, provides an effective defense barrier, through an immune defense system. This human cutaneous system is arbitrarily divided into innate and adaptive components.
The innate immune system is the first nonspecific line of defense and is an active mechanism against invading microorganisms and environmental toxins.
The innate immune response is followed by the acquired immune response, particularly by activation and proliferation of T and B cells to specific antigens.
The outermost layer of the epidermis is the stratum corneum and is made of keratinocytes, cells strongly connected by desmosomes and a hydrophobic cellular matrix, which is a solid anatomical barrier to irritants, allergens and cutting forces.
Supporting the cutaneous physical barrier, there is a system of intrinsic resistance that works with chemical mediators - cytokines - specialized signaling pathways, the complement pathways, leukocyte and antimicrobial peptides (AMPs).
The antimicrobial peptides (AMPs) have been evolutionarily the best preservers of the host´s innate immune defense against bacteria, yeast, parasites (mites), viruses, fungi and tumor cells.
The largest source of AMPs is the keratinocyte. The primary synthesis of AMPs occurs in the stratum granulosum, where they are packaged within lamellar bodies and then transported to the stratum corneum.
Along with keratinocytes, sebocytes, mast cells and neutrophils are the most important sources of AMPs in normal skin. They are also present in saliva and sweat.
In the face of infection, injury or both, neutrophils, mast cells and leukocytes are the largest producers of antimicrobial peptides. The production is triggered by activation of recognition receptors such as toll-like receptors (TLRs), receptors of mannose and helicases. These receptors are activated by lipopolysaccharide from gram-negative bacteria, lipoteichoic acid, peptidoglycans and gram-positive bacteria, yeast and fungi mannans, and nucleic acids of pathogens and residents.
Overproduction of AMPs is related to molecular stimuli due to the increase in the number of receptors of the cell surface, as a secondary response that limits the severity of infection or injury, when the primary line of defense fails.
Physicians should not ignore that CAD is a disease of genetic marking, with in crescendo prevalence, chronic, controllable but incurable, of intricate diagnosis and long-term complex clinical management.
It is thought that in some individuals the initial disturbance (acuity) is an abnormal immune response, and in others, the cause is the dysfunctional epidermal barrier (like - atopic).
In chronic stages in most individuals, the barrier is altered (in synergy between inflammation + secondary infections), but there is also allergic-type reaction.
In the chronic phase, the immune response turns to a T helper-1 pattern, with more IFN-gamma production and perpetuation of pruritic chronic dermatitis (Marseille & Samuelson 2009).
Patients affected with CAD show high incidence of recurrent secondary infections caused by S. pseudointermedius and Malassezia pachydermatis, superinfections with complicated clinical management, synergized by the lack of integrity of the skin barrier, additively potentiated by abnormally low levels of antimicrobial peptides (AMPs) production, which in normal skin have broad-spectrum antimicrobial properties and actions, specifically defensins and cathelicidins B.
These AMPs, cathelicidins and B defensins have antimicrobial and immunomodulatory properties. Their deficiency leads to low immediate defensive response and decreased adaptive response and skin repair processes.
The multiple functions of the AMPs, as "natural antibiotics" and "immune regulators", suggest that they may be promising therapeutic agents.
Increased knowledge and deep understanding of the properties of AMPs may lead to promising new strategies and resources to manage this skin disease in the different affected species.
The clinical management of acute episodes of canine atopic dermatitis (CAD) should include the identification and adequate and effective control of the triggering causes, prescribing baths with the right shampoo for each patient, nutritional balance, supplementation of essential fatty acids, pruritus and skin lesions control using glucocorticoids, or oral oclacitinib and/or topical dermatotherapy.
Regarding chronic canine atopic dermatitis, the first steps must be to identify and avoid seizure-triggering factors, starting by providing proper skin and hair hygiene for the patients. These should include more frequent baths (warm water), avoiding additive dehydration. Supply essential fatty acids orally.
The most effective medications to reduce chronic pruritus and lesions from recurrent dermatitis (chronic) are steroids, cyclosporine and oral oclacitinib, as well as topical corticosteroids.
Moreover, the treatment of CAD must be polymodal with multifactorial coverage and treatment regimens vary among individuals, as well as different stages of the disease in the same individual.
References
1. Olivry T, DeBoer DJ, Favrot C, et al. Treatment of canine atopic dermatitis: 2010 clinical practice guidelines from the International Task Force on Canine Atopic Dermatitis. Veterinary Dermatology. 2010;21:233–248.
2. Olivry T, Bizikova P. A systematic review of randomized controlled trials for prevention or treatment of atopic dermatitis in dogs: 2008–2011 update. Veterinary Dermatology. 2013;24:97–117.
3. Paller AS, Simpson EL, Eichenfield LF, et al. Treatment strategies for atopic dermatitis: optimizing the available therapeutic options. Seminars in Cutaneous Medicine and Surgery. 2012;31(3 Suppl):S10–7.
4. Nuttall TJ, McEwan NA, Bensignor E, et al. Comparable efficacy of a topical 0.0584% hydrocortisone aceponate spray and oral ciclosporin in treating canine atopic dermatitis. Veterinary Dermatology. 2012;23:4–10.
5. Bloom P. Nonsteroidal, nonimmunosuppressive therapies for pruritus. Veterinary Clinics of North America: Small Animal Practice. 2013;43:173–187.
6. Valdman-Grinshpoun Y, Ben-Amitai D, Zvulunov A. Barrier-restoring therapies in atopic dermatitis: current approaches and future perspectives. Dermatology Research and Practice. 2012;2012 Article ID 923134.
7. Marsella R. Fixing the skin barrier: past, present and future - man and dog compared. Veterinary Dermatology. 2013;24:73–6.