Clinical inmunodermatology in small animals

PRESENTATION BROCHURE Fernando Fariñas Guerrero Carlos Vich Cordón

CLINICAL IMMUNODERMATOLOGY in small animals

CLINICAL IMMUNODERMATOLOGY in small animals

Fernando Fariñas Guerrero Carlos Vich Cordón

Fernando Fariñas Guerrero Carlos Vich Cordón

CLINICAL IMMUNODERMATOLOGY in small animals Fernando Fariñas Guerrero Carlos Vich Cordón

CLINICAL IMMUNODERMATOLOGY in small animals

Clinical immunodermatology in small animals

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AUTHORS: Fernando Fariñas Guerrero,

Carlos Vich Cordón.

FORMAT: 17 x 24.

NUMBER OF PAGES: 216.

NUMBER OF IMAGES: 200.

BINDING: hardcover.

RETAIL PRICE

70 €

eBook included

Servet presents this innovative work written by two specialists in the field. A unique feature of this book is that it takes a holistic approach to the fields of dermatology and immunology, rather than approaching them as distinct subjects. In this way, different dermatoses are presented considering the corresponding immunological, immunopathological, and immunophysiological features. The combination of the two subjects makes this work an indispensable tool for readers, providing them with guidelines to tackle each pathology that are unique within the current literature.

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Clinical immunodermatology in small animals

Presentation of the book This book is the result of a collaboration between Fernando and Carlos who, driven their respective passions for immunology and dermatology, sought to create a complete overview of dermatoses with a particular emphasis on the immunological bases of these conditions.

The authors discuss the immunological, immunopathological and immunophysiological aspects of each of the selected dermatoses, as well as clinical features such as topography, lesion type, diagnostic methods and case descriptions, which are so crucial to the daily clinical experience.

The close friendship between the two authors, who even lecture together, has helped them combine their respective field of immunology and dermatology. This provides the reader with a set of tools with which to tackle each type of dermatosis that is unique among the current literature.

The authors Carlos Vich Cordón Carlos Vich Cordón received his degree in Veterinary Medicine from the Universitat Autònoma, Barcelona, in June 1995. He is a diplomate in Dermatology of the European School for Advanced Veterinary Studies (ESAVS; Luxembourg, 1996 and 1997; Barcelona, 1998) and a member of the European Society of Veterinary Dermatology (ESVD) since 1995. He trained from September 1995 to August 1996 at the Clínica Veterinaria Papiniano in Milan under Dr. Fabrizio Fabbrini (Full Member ESVD). He worked as an emergency veterinarian from September 1996 to March 1997 at the Societat de Serveis Veterinaris, Barcelona.

In 1996 he founded Servei de Dermatología Veterinària (DERMOVET), which currently visits over 450 clinics throughout Catalonia, Spain, and Portugal. Currently he is the head of the Department of Dermatology at Societat de Serveis Veterinari.

He is also author of the books Feline Dermatology: about 50 Clinical Cases, and Canine ­Dermatology: about 50 Clinical Cases. He has given over 300 presentations throughout Spain, Portugal, and South America.

Clinical immunodermatology in small animals

Fernando Fariñas Guerrero Fernando Fariñas Guerrero holds graduate and doctoral degrees in medicine (Clinical Neuroimmunology), veterinary medicine (Respiratory Immunopathology) and biology (Basic Aspects of Thymus Development). Within the field of internal medicine, he specialises in clinical immunology and infectious diseases, with a specific focus on anatomical pathology, in particular infectious pathology, haematopathology, and immunopathology, with experience and knowledge acquired in leading international centres of reference in these fields.

He is the founder and president of Fundación IO, which is dedicated to developing international projects to combat outbreaks of zoonoses and emerging infectious diseases.

He holds an international diploma in Tropical Medicine and Leprology, and is primarily devoted to the study of infectious pathologies (zoonotic diseases) and, within the field of clinical immunology, immunoinfectology, vaccinology, immunonutrition, autoimmunity, and immunodeficiencies.

He serves as a veterinary and medical advisor to various public and private agencies at both national and international levels, and is a member of specialised study groups of the International Federation of Immunology focused on the fields of immunotherapy (GEIT) and immunodeficiencies (GEID), as well as various groups involved in the study of vectorborne diseases and zoonoses.

He has presented his work at numerous conferences, Master’s courses, and specialised courses in the fields of clinical immunology, infectious diseases, and vaccinology.

He is a member of the editorial board of several national and international journals. He has authored several books and numerous articles, and is currently the director of the Spanish Institute of Clinical Immunology and Infectious Diseases. He also currently holds the post of President of the “Ynmun” Association, which studies immunological and infectious diseases. His next book is a popular science publication, which will be published in the coming months, entitled In Self Defence: Adventures and Misadventures of the Immune System (in Spanish).

He has received numerous national and international awards in the fields of medicine and veterinary science.

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Fernando Fariñas Guerrero Carlos Vich Cordón

CLINICAL IMMUNODERMATOLOGY in small animals

CLINICAL IMMUNODERMATOLOGY in small animals

Fernando Fariñas Guerrero Carlos Vich Cordón

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Table of contents 1. Basic cutaneous immunology and immunopathology Skin immunity A brief introduction to the immune response Types of immunological hypersensitivity Diagnosis of dermatological allergies Desensitisation immunotherapy Immunodeficiencies and dermatosis Immunomodulators in dermatology

2. Introduction to clinical dermatology Introduction to clinical dermatology Clinical dermatology terminology Skin cytology

3. Immune-mediated skin diseases

Pemphigus foliaceus. Clinical case Discoid lupus erythematosus.

Clinical case Dermatomyositis. Clinical case Uveodermatologic syndrome.

Clinical case Vitiligo. Clinical case Erythema multiforme and toxic epidermal necrolysis. Clinical case Sebaceous adenitis. Clinical case Lymphocytic folliculitis (alopecia areata and pseudopelade). Clinical case Plasma cell or lymphoplasmacytic pododermatitis. Clinical case Idiopathic sterile granuloma and pyogranuloma. Clinical case Postinflammatory hyperpigmentation/ hypopigmentation. Clinical case Skin reactions to drugs and vaccines.

Clinical case

Atopic dermatitis. Clinical case

Panniculitis and cellulitis. Clinical case

Food allergy. Clinical case

Lupoid onychodystrophy. Clinical case

Angioedema and urticaria. Clinical case Flea allergy dermatitis. Clinical case Arthropod bite hypersensitivity.

Clinical case

4. Cutaneous neoplasms of immune origin Histiocytoma. Clinical case

Eosinophilic granuloma. Clinical case

Canine mastocytoma. Clinical case

Contact hypersensitivity. Clinical case

Cutaneous lymphoma. Clinical case

Cutaneous vasculitis. Clinical case

Melanoma. Clinical case

Intraepidermal lymphocytes

Melanocyte

Dendritic cell

Fibroblasts

Epidermotropic lymphocytes Macrophage

Vascular endothelium

Mast cell

Basic cutaneous immunology and immunopathology

Langerhans cell

Keratinocytes

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In 1978, Streilein proposed that skin immunity is mediated by a highly specialised system, and introduced the concept of “skin-associated lymphoid tissue” (SALT). This is composed of cells that reside in the epidermis and dermis. For example, the perivascular area of the postcapillary venules of the papillary dermis contains a high concentration of cells implicated in the immune response (mast cells, macrophages, dendritic cells, and T lymphocytes).

This anatomical location, known as the dermal perivascular unit, is a site of great activity during inflammatory processes. The concerted action of the various cellular elements of the SALT provides the skin with immune protection against external aggression and the development of skin tumours. In summary, the immune activity of the skin is mediated via mechanisms involving cells that reside in the skin as well as others that are shared with other tissues and systems (Fig. 1).

Skin immunity

THE SALT CONCEPT

FIGURE 1. Types of immunological cells in the skin.

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CELLS COMPRISING THE SALT Keratinocytes Keratinocytes (Fig. 2) account for 90 % of epidermal cells and are an effective defence against the external environment. However, these cells also act as accessory cells that participate in the immune response through the release of cytokines and the expression of adhesion molecules that regulate the movement of immunocompetent cells. In normal, noninflamed skin, keratinocytes express only MHC class I molecules. Conversely, in inflamed skin interferon-gamma (IFN-γ)-producing T cells can induce keratinocyte expression of MHC class I and II molecules, thus converting them into true antigen-presenting cells. Furthermore, keratinocytes are responsible for the production of the aforementioned cutaneous antimicrobial molecules (defensins, cathelicidins, etc.).

FIGURE 2.

Histology of the epidermis, showing various layers of keratinocytes.

Epidermotropic lymphocytes A specific subset of memory T cells has the ability to preferentially move from the bloodstream into the skin. This group of T lymphocytes is identified by a marker known as cutaneous lymphocyte-associated antigen (CLA), and is generated in lymphatic ganglia and regional lymph nodes of the skin. Although their function is immune surveillance, CLA+ T lymphocytes have been implicated in the pathogenesis of certain skin conditions, including cutaneous lymphoma, allergic contact dermatitis, atopic dermatitis, alopecia areata, and vitiligo.

In normal skin, CLA+ T lymphocytes constitute between 5 % and 10 % of all T lymphocytes, but this proportion increases to between 80 % and 90 % in the event of inflammation (Fig. 3).

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Antigen-presenting cells (APCs) are a heterogeneous group of cells with the ability to present antigens to T lymphocytes.

However, not all APCs have the same antigen-presenting capacity. Dendritic cells are the most efficient of all APCs in presenting antigens during the primary response. Langerhans cells (Fig. 4) belong to a large family of dendritic cells and are the most important APCs in the skin, constituting between 2 % and 8 % of

FIGURE 4.

Langerhans cells embedded between keratinocytes.

Note the “dendritic” morphology, which resembes that of a nerve cell.

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Skin immunity

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Langerhans cells

Basic cutaneous immunology and immunopathology

FIGURE 3.

Intraepidermal lymphocytes, occupying the spaces between keratinocytes.

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the cells present in the epidermal layer. Derived from bone marrow, these cells are located in the basal and suprabasal layers of the epidermis, where they form a vast network of cells capable of taking up antigen. After making contact with the antigen, Langerhans cells can shuttle the antigen by migrating from the dermis to regional lymph nodes via the afferent lymphatic vessels. In normal, noninflamed skin these are the only cells capable of constitutively expressing MHC class II molecules on their cell surface. These molecules are necessary for the stimulation of the T cell-dependent immune response. In this regard, Langerhans cells play a double role in antigen presentation: they present antigens to naive T cells in the lymph node during the induction phase of the immune response, and to memory T cells during the effector phase of the cutaneous immune response. Currently, there is some debate as to the role of these cells in promoting immunosuppression and inducing antigen tolerance in the skin, with some authors suggesting that they favour more anti-inflammatory than inflammatory responses.

Melanocytes Although melanocytes (Fig. 5) have not traditionally been ascribed an immune function, in recent years it has been proposed that these cells may play an important role in the immune activity of the skin. They are located in the basal layer of the epidermis, very close to the dermis, and can produce several cytokines that act as mediators of inflammatory processes in the skin.

FIGUREÂ 5.

Epidermal melanocytes.

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Macrophages

Macrophages are a heterogeneous and diverse population of cells that help maintain skin homeostasis and integrity.

In addition to defending against infections, they are key cellular activators of healing processes and scar tissue formation. These activated macrophages have the ability to phagocytose and release large amounts of lytic enzymes.

Macrophages usually have a physiological function, removing dead or aging cells and playing an important role in innate immunity in response to invading microorganisms, which they can phagocytose, lyse, and eliminate. Therefore, these cells constitute an important sentinel population crucial for the control of invading pathogens and the repair of damaged tissue. The inappropriate activation of these cells can lead to the production of proinflammatory cytokines and, consequently, the development of inflammatory skin conditions. In the skin, macrophages may be associated with the dermal perivascular unit, where they regulate the processes of extravasation of inflammatory cells. They can also be associated with lymphatic vessels, regulating lymphangiogenesis, or may reside in the interstitial space of the dermis, removing tissue debris for degradation or remodelling the cellular environment.

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Basic cutaneous immunology and immunopathology

FIGUREÂ 6.

Macrophages.

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Skin immunity

Circulating monocytes that reside in tissues are converted into tissue macrophages (Fig. 6) and can be activated by certain stimuli such as bacterial endotoxins, IFN-γ, and complement fragment C3b.

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Mast cells Given their presence in the dermal perivascular unit in normal skin and their multiple functions mediated via the release of mediators during inflammation, a brief summary of the characteristics and functions of mast cells is provided here. Mast cells (Fig. 7) originate in the bone marrow, pass into the blood as immature cells, and undergo maturation and differentiation in tissues under the influence of various factors in the microenvironment.

Immunohistochemical studies have shown that there are two mast cell phenotypic variants in tissue, characterised by their content of neutral proteases.

The MCT phenotype contains only tryptase, while the MCTC phenotype contains tryptase and chymase. The former are found predominantly in the mucosa and the latter in connective tissue. These cells can produce and release multiple biologically active mediators, including histamine, heparin, tryptase, chymase, carboxypeptidase, TNF-α, and other proinflammatory cytokines.

Mast cells can be activated and induced to release various mediators by different mechanisms: • Antibodies: mainly IgE. • Neuropeptides: such as substance P. • Anaphylatoxins: C3a, C5a.

• Cytokines.

• Physical stimuli: heat, cold, exercise, ultraviolet radiation, etc.

• Psychological stimuli: stress.

• Medication.

FIGURE 7.

Mast cells.

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Mast cells are mostly known as cellular effectors of Th2 responses, which are predominantly associated with allergic hypersensitivity phenomena. However, they also defend against certain pathogens and participate in scar formation and wound healing, and are involved in maintaining homeostasis, with a demonstrated ability to undergo activation in situations of hypoxia and nutrient deficit at the tissue level.

Mast cell survival and development is dependent upon the expression of the receptor c-Kit. As discussed in the chapter on mast cells, c-Kit is a marker used in the cytological and histological gradation of mast cell tumours.

Dermal plasmacytoid dendritic cells (pDCs) The dermis also hosts other types of dendritic cells, including pDCs, which primarily specialise in the response to nucleic acids derived from viruses and bacteria (especially viral RNA and bacterial DNA).

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Basic cutaneous immunology and immunopathology

Specialised DDCs are a group of antigen-presenting cells specialised in “antigen cross-presentation�, which allows the development of highly efficient adaptive immune responses. This cross-presentation phenomenon is based on the simultaneous activation of a cellular and humoural response to the antigen. Cross-presentation of noninfectious antigens can give rise to immunological tolerance to the antigens in question. By contrast, if the antigens are infectious in origin (natural or vaccine-derived), cross-presentation results in the development of an effective immune response. The importance of specialised DDCs is underscored by the pharmaceutical industry’s current efforts to design new approaches to vaccine administration that generate the largest possible number of antigens to these DDCs, in order to effectively activate DDCs and thus obtain maximum benefit in terms of producing a cross-reactive immune response. Importantly, these cells can be activated by smaller amounts of antigen than those used in conventional vaccines, thereby diminishing considerably the risk of adverse reactions.

Skin immunity

Specialised dermal dendritic cells (DDCs)

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Food allergy This is an allergic reaction to a component of the diet. It can trigger different hypersensitivity reactions: type I, type III, or type IV. There is considerable variation in the foods that cause food allergy. These include foods of meat (chicken, beef, lamb) and/or vegetable (soy) origin, and those that contain fish protein (e.g. salmon), as well as those that contain histamine (e.g. fermented cheese, pork liver, tuna, spinach, white eggs, chocolate, blue fish, strawberries, tomatoes), which facilitates the establishment of an inflammatory reaction.

Cross reactions can also occur in response to distinct proteins with specific similarities (e.g. poultry and ruminant proteins, which share approximately 70 % sequence homology similarities). Proteins that mediate this phenomenon are known as panallergens.

CLINICAL PRESENTATION The age of onset of clinical signs of food allergy varies greatly. One third of patients with this disease begin to show signs before 1 year of age; however, like atopy, this condition can affect animals of any age.

The key clinical sign of food allergy is nonseasonal pruritus.

Pruritus can be severe (10 on a scale of 1 to 10); affected animals can scratch, bite, or lick themselves continuously for 24 hours, much to the despair of their owners. In addition, patients often lose weight due to improper absorption of food, constant metabolic activation, and the energetic cost of continuous intense pruritus.

Food allergies account for about 5 % of cases of cats and dogs with dermatological signs and 15 % of all allergic patients.

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FIGURE 1. Perianal itching.

FIGURE 2. Perianal dermatitis with lichenification and hyperpigmentation.

Cutaneous clinical signs are commonly accompanied by digestive signs, due to the animal’s ingestion of the allergens, which in this case are called trophoallergens. Digestive signs appear in 10 % to 15 % of cases, and include vomiting, diarrhoea, colitis with the presence of mucus (and in some cases fresh blood), pasty stools, and tenesmus. These digestive signs are caused by inflammation of the intestinal mucosa, and subsequent alterations in cell membranes and enterocyte permeability. This is accompanied by destruction of the villi, causing the patient to become vulnerable to the antigens and cytokines present in the bloodstream.

In addition to gastrointestinal signs, neurological signs may be observed in some cases, even including seizures and behavioural changes (e.g. irritability).

Occasionally, affected animals may show respiratory signs and reactive lymphadenopathy, the latter a result of the immune system’s exaggerated response (mass production of antibodies).

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Immune-mediated skin diseases

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Food allergy

Anal and perianal pruritus in both dogs and cats is also highly characteristic of food allergy (Figs. 1 and 2). Perianal eosinophilic plaques may be observed in cats.

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FIGURE 3. Otitis externa with obstruction of the ear canal.

On the other hand, external otitis (unilateral or bilateral) is frequently the only clinical sign, accompanied by marked hyperplasia of the external ear canal, and in many cases stenosis or obstruction of the ear canal (Fig. 3).

While otitis and pododermatitis can be observed in both food allergy and atopy, the clinical presentation of food allergy tends to be much more severe than that of atopy.

The difference between food allergy and intolerance is that the latter is largely characterised by gastrointestinal signs, particularly diarrhoea, without the presence of cutaneous signs.

LESION TOPOGRAPHY Lesion topography is not as clear as in cases of atopy, as the lesions are not caused by direct contact between the skin and the allergen. However, food allergy can be easily mistaken for atopy. Nonetheless, in this author’s experience, pruritus tends to be much more intense in cases of food allergies.

Although the allergen is ingested in food allergies, it can also affect the facial area (Fig. 4), the dorsal aspect of the extremities, the perianal area and the ventral aspect of the tail base, and the axillae, abdomen, and external ear canal.

However, in many cases lesions are observed across the entire body surface.

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Food allergy

TYPES OF LESIONS The most common lesions include erythematous macules, erythema, plaques, papules, and wheals.

Lesions caused by self-trauma, in response to intense pruritus, are commonly seen. These include excoriations, erosions, and ulcers, as well as chronic lesions such as hyperpigmentation, lichenification, and seborrhoea.

Erythema multiforme, caused by the intense immune system reaction, has also been described.

DIAGNOSIS

Immune-mediated skin diseases

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FIGURE 4. Cat with food allergy showing cutaneous clinical signs on the face.

Three different approaches can be used to diagnose food allergy: 1) Put the patient on a restricted diet, preferably prepared by the owner at home, for 8 to 12 weeks, which is sufficient time to observe a positive response.

Next, return the patient to their previous diet. This should result in the return of the clinical signs, allowing identification of the causative trophoallergen(s).

2) Provide the patient with a hydrolysed protein diet consisting of proteins that are of less than 6 kD and are thus unable to trigger mast cell degranulation.

3) Radically change the patient’s source of protein. If the animal consumes dry food based on terrestrial protein, the diet can be switched to one based on marine protein, or vice versa.

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CLINICAL CASE

Food allergy Medical history • One-year-old Yorkshire terrier, fully vaccinated and dewormed (Fig. 5).

• Lives with one other dog that shows no dermatological signs.

FIGURE 5.

Yorkshire terrier with suspected food allergy.

Case history The patient presents with chronic generalised pruritic dermatosis with intense anal and perianal pruritus. The dog had previously experienced several episodes of pruritus and pyoderma, but now fails to respond as before to prednisone and antibiotic treatment.

For the previous two months, the dog’s stool has been pasty, with the presence of mucus. The stool test is negative.

In the general physical examination all parameters are within the physiological range.

Dermatological consultation Pustules, epidermal collarettes, and crusts are observed in the dermatological examination (Fig. 6). Erythema, lichenification, and hyperpigmentation is evident on the ventral aspect of the tail and in the anal and perianal regions (Fig. 7).

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The publishing strength of Grupo AsĂ­s Editorial Servet, a division of Grupo AsĂ­s, has become one of the reference publishing companies in the veterinary sector worldwide. More than 15 years of experience in the publishing of contents about veterinary medicine guarantees the quality of its work. With a wide national and international distribution, the books in its catalogue are present in many different countries and have been translated into nine languages to date: English, French, Portuguese, German, Italian, Turkish, Japanese, Russian and Chinese.

Its identifying characteristic is a large multidisciplinary team formed by doctors and graduates in Veterinary Medicine and Fine Arts, and specialised designers with a great knowledge of the sector in which they work. Every book is subject to thorough technical and linguistic reviews and analyses, which allow the creation of works with a unique design and excellent contents.

Servet works with the most renowned national and international authors to include the topics most demanded by veterinary surgeons in its catalogue. In addition to its own works, Servet also prepares books for companies and the main multinational companies in the sector are among its clients.

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