Diagnostics and Therapy in Veterinary Dermatology E-Book
152,99 €
Mehr erfahren.
- Herausgeber: John Wiley & Sons
- Kategorie: Fachliteratur
- Sprache: Englisch
Diagnostics and Therapy in Veterinary Dermatology presents thorough coverage of the latest discoveries, drugs, and treatments for dermatologic conditions in animals. Chapters written by experts in each respective area of veterinary dermatology contain up-to-date information on new diagnostic tools and tests, autoimmune diseases, parasitic and fungal infections, medical management of acute and chronic conditions, alternative dermatologic therapies, and more. Offering practical solutions for both specialist and general practice veterinarians dealing with dermatology cases, this wide-ranging resource also addresses antibiotic resistance and misuse, the availability of foods for elimination diet trials, problems with generic drugs, emerging infectious diseases, and other important problems currently facing the profession. Throughout the text, veterinary practitioners are provided with real-world guidance on improving how they work up their dermatology cases and strengthening communication between the primary care veterinarian and the dermatologist. Edited by a leading board-certified dermatologist, this volume: * Focuses on cats and dogs * Includes numerous high-quality clinical photographs illustrating all key concepts * Covers topics such as how to use your nursing staff to the fullest, the One Health movement, and how changing climate is increasing the spread of certain dermatologic diseases * Discusses approaches for building a better working relationship between clients, primary care veterinarians and dermatologists * Provides insights on the future of technology in the diagnosis and treatment of dermatologic diseases Covering the very latest developments in the field, Diagnostics and Therapy in Veterinary Dermatology is essential reading for veterinary dermatologists, veterinary students, and any veterinary general practitioner with a dermatology caseload.
Sie lesen das E-Book in den Legimi-Apps auf:
Seitenzahl: 674
Veröffentlichungsjahr: 2021
Ähnliche
Table of Contents
Cover
Title Page
Copyright Page
Acknowledgments
Foreword
List of Contributors
1 The Skin as an Immune Organ
Immune System of the Skin
Epidermis
Dermis
Subcutis
Defense from Harmful Substances
Dysfunction of the Immune System
Recommended Reading
2 How to Get the Most Out of Your Dermatologic History and Examination
Dermatologic History
Dermatologic Examination
Recording Results
3 New Diagnostic Tools and Tests for Dermatology
The Importance of Diagnostic Investigations in Dermatology
Molecular Diagnostic Tests: How Do They Work and What Is Available?
Serology
Primary Binding Tests
Secondary Binding Tests
Tertiary Binding Tests
Polymerase Chain Reaction
Pulsed‐Field Gel Electrophoresis
Transmission Electron Microscopy
Whole‐Genome Sequencing
Matrix‐Assisted Laser Desorption Ionization‐Time of Flight Mass Spectrometry
Conclusion
References
4 When, Where, and How to Biopsy Skin
When
Where
How
Where to Send
Recommended Reading
5 Antimicrobial‐Resistant Staphylococcal Infection
Staphylococcus
spp. Associated with Skin Infections
Staphylococcal Antimicrobial Resistance Mechanisms
Risk Factors for Acquisition of Methicillin‐Resistant Staphylococci
Culture and Antimicrobial Susceptibility Testing
Treatment of Antimicrobial‐Resistant Staphylococcal Infections
Restriction‐of‐Use Policy
Future Directions for Treatment of Antimicrobial‐Resistant Staphylococcal Infections
Conclusion
Recommended Reading
References
6 Fungal and Oomycete Infections
Dermatophytosis
Malassezia
Oomycetes
Subcutaneous Mycoses
References
7 Parasitic Infections
Canine Scabies
Feline
Scabies
Canine Demodicosis
Feline Demodicosis
Lice
Ticks
Fleas
Recommended Reading
8 Emerging Infectious Diseases in Veterinary Dermatology
Canine and Feline Cutaneous Leishmaniasis
Sporotrichosis
Bartonellosis
Recommended Reading
References
9 Canine Hypersensitivities
History
Physical Exam
Atopic Dermatitis
Food “Allergy”
Contact Allergy
Insect Bite Allergies
Recommended Reading
References
10 Feline Hypersensitivities
What Does a Hypersensitive Cat Look Like?
Symmetric, Initially Nonlesional Pruritus with Subsequent Trauma and Hypotrichosis or Alopecia
Papular Crusting Dermatitis (Miliary Dermatitis)
Otitis
Eosinophilic Granuloma Complex
Diagnostic Workup
Diagnosis
Cat Still Has Problems: How to Further Narrow Down the Diagnosis
Environmental Triggers
Controlling Clinical Signs during the Diagnostic Workup
Disorders That May Be Confused with Feline Hypersensitivity Diseases
Recommended Reading
References
11 Common and Emerging Autoimmune Diseases
Pemphigus Foliaceus
Sebaceous Adenitis
Sterile Nodular Panniculitis
Symmetric Lupoid Onychodystrophy, Symmetric Onychomadesis
Proliferative Thrombovascular Necrosis of the Pinnae
Cutaneous Vasculitis
Erythema Multiforme
Ischemic Dermatopathies
Recommended Reading
References
12 Endocrine and Metabolic Diseases with Dermatologic Manifestations
Hypothyroidism
Feline Hyperthyroidism
Canine Hypercortisolism
Feline Hypercortisolism
Sex Hormone Dermatoses
Cutaneous Xanthomas
Hepatocutaneous Syndrome
Zinc‐Responsive Dermatosis
Alopecia X
Recommended Reading
References
13 Medical Management of Acute and Chronic Otitis
Acute Otitis
Chronic Otitis
When to Refer
Recommended Reading
References
14 What Is the Difference between Brand Name, Generic, and Compounded Drugs?
Drugs Approved by the US Food and Drug Administration
Generic Drugs
Compounded Drugs
References
15 Topical Therapies
Anti‐infectious
Antipruritics
Antiseborrheic
Barrier Repair
Immunoregulators
Application
Recommended Reading
References
16 Antimicrobial Resistance
Determinants of Antimicrobial Resistance
Determination of Susceptibility or Resistance
Mutant Prevention Concentration
Antibiotic Classes and Resistance Mechanisms
Advances in Laboratory Diagnostics and Their Impact on Antibiotic Resistance
Conclusions
Recommended Reading
References
17 Omega‐3 Fatty Acids
Recommended Reading
References
18 Immunopharmacology
Drugs That Affect Innate Immunity
Drugs That Affect the Bridge between Innate and Adaptive Immunity
Drugs That Affect Adaptive Immunity
Undefined Mechanisms (Anti‐inflammatory, Regulatory, Other)
Recommended Reading
19 Allergen Immunotherapy
Mode of Action
Indications for Allergen Immunotherapy
Testing and Selection of Allergens for the Extract
Adverse Effects of Allergen Immunotherapy
Route of Administration
Conclusions
Recommended Reading
References
20 Biologic Therapies for Dermatologic Use
Monoclonal Antibodies in Veterinary Dermatology
DNA Vaccination
Intravenous Immunoglobulin
Interferons
Staphylococcal Bacterins
Conclusions
References
21 Use of Lasers in Dermatology
Diode Lasers
CO
2
Lasers
Laser Safety
Considerations for Laser Usage
Neoplastic Conditions
Ears
Infectious Diseases
Inflammatory Conditions
Recommended Reading
22 Unconventional and Plant‐Based Therapies
Homeopathy
Photobiomodulation
Platelet‐Rich Plasma
Probiotics
Plant‐Based Therapies
Topical Therapies
References
23 Sedation, Anesthesia, and Pain Management in Small Animal Dermatology
Sedation
Skin Testing
General Anesthesia
Monitoring
Local Anesthesia
Topical Local Anesthesia
Local Infiltration
Ring Block
Pain Management
Conclusions
References
24 How Your Nursing Staff Can Improve Efficiency and Compliance in the Management of Dermatologic Cases
History Taking
Intake Interview
Pruritus Scale
Diagnostic Testing
Patient Discharge
Patient Follow‐Up Telephone Calls
Conclusions
References
25 Communication Between the Client, Primary Care Practitioner, and Dermatologist
Communication with the Pet Family
Initiating the Session
Gathering Information
Physical Examination
Explanation and Planning
Closing the Session
Collaboration Between Primary Care and Specialist Veterinarians
Attitudes and Perceptions of Primary Care Veterinarians Regarding Referral to a Specialist
Building a Collaborative Relationship: For Primary Care Veterinarians
Building a Collaborative Relationship: For Specialists
Inter‐Practice Communication and Skills
The Pet Family’s Role in Communication
Conclusions
Recommended Reading
References
26 The Future of Technology and Computers in Veterinary Medicine
Electronic Medical Records
Behavioral and Physiologic Monitoring
Current Research and Future Opportunities
Off‐Body Technologies for Tracking Activity, Behavior, and Physiologic Changes
On‐Body, Wearable Activity, Behavior, and Physiologic Trackers
In‐Body Activity, Behavior, and Physiologic Tracking
Benefits of Behavioral and Physiologic Tracking
Challenges in Behavioral and Physiologic Tracking
Conclusions
References
Index
End User License Agreement
List of Tables
Chapter 1
Table 1.1 Cells of the innate and adaptive immune system discussed in this ...
Chapter 3
Table 3.1 Common diagnostic tests available in veterinary dermatology. This...
Chapter 5
Table 5.1 Example of methicillin‐resistant
Staphylococcus pseudintermedius
s...
Table 5.2 Potential systemic antimicrobial options for treatment of antimic...
Chapter 6
Table 6.1 Laboratories for oomycete/fungal diagnostics.
a
Chapter 8
Table 8.1 Clinical staging of canine and feline leishmaniasis.
Table 8.2 Approved drugs for the treatment of canine and feline leishmanias...
Table 8.3 Antifungal drugs with high to moderate
in vitro
activity against
S
...
Table 8.4 Treatments for canine and feline sporotrichosis.
Table 8.5
Bartonella
species found in cats and dogs.
Table 8.6 Clinical signs associated with common
Bartonella s
pecies.
Table 8.7 Reported treatments for bartonellosis in cats and dogs.
Chapter 9
Table 9.1 List of major therapeutics for atopic dermatitis.
Chapter 10
Table 10.1 Clinical reaction patterns in hypersensitive cats.
Table 10.2 Recommended antibiotic doses for cats.
Table 10.3 Diagnostic criteria for nonflea feline hypersensitivity.
Table 10.4 Recommended antihistamine doses for cats.
Chapter 11
Table 11.1 Dosing of immunosuppressive medications for autoimmune diseases.
Table 11.2 Sample glucocorticoid tapering schedule.
Table 11.3 Diagnostic ruleouts for sterile pyogranulomatous panniculitis.
Chapter 12
Table 12.1 Medications that affect thyroid diagnostic testing.
Table 12.2 Interpretations of thyroid diagnostic testing results.
Chapter 13
Table 13.1 Definition of acute and chronic otitis.
Table 13.2 Underlying causes of otitis.
Chapter 16
Table 16.1 Contributors to antimicrobial resistance.
Table 16.2 Enzymatic Comprehensive list of historical and contemporary anti...
Table 16.3 Potential impact of antimicrobial drug resistance.
Table 16.4 Practices to decrease antibiotic resistance now.
Chapter 18
Table 18.1 Commonly used oral glucocorticoids in the dog.
Table 18.2 Commonly used oral glucocorticoids in the cat.
Chapter 19
Table 19.1 Drug withdrawal times prior intradermal testing.
Chapter 22
Table 22.1 Indications for photobiomodulation.
Chapter 23
Table 23.1 Drugs that can be used for sedating dermatologic patients.
Table 23.2 Suitability of sedative drugs for skin testing in small animals.
Table 23.3 Induction agents for dermatologic patients.
Table 23.4 Recommended maximum dose for the commonly used local anesthetics...
Table 23.5 Nonsteroidal anti‐inflammatory drugs (NSAIDs) approved for dogs ...
List of Illustrations
Chapter 1
Figure 1.1 Innate skin immune system. 1. The innate immune system is activat...
Figure 1.2 Adaptive skin immune system. 1. Langerhans cells (LCs) are activa...
Chapter 2
Figure 2.1 Example of a dermatology history form for a client.
Figure 2.2 A visual analog scale for owners to report their pet’s level of p...
Figure 2.3 Depigmentation, erosion, erythema, and loss of normal cobblestone...
Figure 2.4 Hyperkeratosis, crusting, and erythema of the paw pads of a dog....
Figure 2.5 Epidermal collarettes, pustules, erythema, and hyperpigmentation ...
Figure 2.6 Alopecia, crusting, and hyperpigmentation along the pinnal margin...
Figure 2.7 Ulcerations, draining tracts, and scarring in the inguinal region...
Figure 2.8 Perianal erythema in a dog with food allergy.
Figure 2.9 Dog with chronic solar dermatitis. Multifocal areas of erythema a...
Chapter 3
Figure 3.1 Direct ELISA. In the first stage the antigen (orange triangle) fr...
Figure 3.2 Indirect ELISA. The antigen (orange triangle) is adhered to the p...
Figure 3.3 Sandwich ELISA. Monoclonal antibody (yellow) for the antigen that...
Chapter 4
Figure 4.1 Noninfectious diseases that should be biopsied.
Figure 4.2 Nodular lesions that should be biopsied and cultured.
Figure 4.3 Primary lesions.
Figure 4.4 Secondary lesions.
Figure 4.5 Appropriate sampling. (a) Inappropriately taken biopsy punch with...
Figure 4.6 Punch biopsy. (a) Instrumentation for punch biopsy. (b) Inject li...
Figure 4.7 Double punch. (a) Rapidly growing mycobacteriosis. (b) Lateral vi...
Chapter 5
Figure 5.1 Inguinal area of a dog with superficial pyoderma. Note the papule...
Figure 5.4 Multiple alopecic annular lesions with mild hyperpigmentation in ...
Figure 5.5 Paw of a dog with two large interdigital furuncles (deep pyoderma...
Figure 5.6 Deep pyoderma in an acral lick granuloma on the fore limb of a do...
Figure 5.7 (a) Large intact pustules and epidermal collarettes on the ventra...
Figure 5.8 Collection of a culture sample from beneath a crust in a dog with...
Figure 5.9 Collection of a sterile punch biopsy for tissue culture following...
Chapter 6
Figure 6.1 (a) Example of an epidermal collarette from a dog with bacterial ...
Figure 6.2 Generalized dermatophytosis – multifocal to diffuse erythema, alo...
Figure 6.3 Young dog with a focal well‐circumscribed patch of erythema, alop...
Figure 6.4 Dog with alopecic scaling lesion on the face (
Trichophyton mentag
...
Figure 6.5 Dermatophytosis and onychomycosis caused by
Microsporum gypseum
....
Figure 6.6 Kitten with generalized
Microsporum canis
; note erythema, alopeci...
Figure 6.7 Focal area of alopecia and crusting just above the nasal planum i...
Figure 6.8 Dog with a kerion (
Microsporum gypseum
) on the dorsal muzzle – a ...
Figure 6.9 Apple‐green fluorescence of
Microsporum canis
under Wood’s lamp....
Figure 6.10 Ectothrix arthrospores (blue arrow) surround the outside of the ...
Figure 6.11 (a)
Dermatophyte test medium
() plate with red color change asso...
Figure 6.12 (a)
Microsporum canis
macroconidia – spindle shaped with thick, ...
Figure 6.13 Dog with
Malassezia
pododermatitis: lichenification, hyperpigmen...
Figure 6.14 Mixed‐breed dog with
Malassezia
dermatitis: severe lichenificati...
Figure 6.15 13‐year‐old cat with paraneoplastic alopecia. Both hind paws and...
Figure 6.16 German shepherd with pythiosis: multiple nodules and draining tr...
Figure 6.17 Large granulomatous lesion on the tail along with a smaller lesi...
Figure 6.18 Large granulomatous lesion on the paw of a dog with lagenidiosis...
Figure 6.19 Diff‐Quik–stained touch prep from a dog with a draining tract on...
Figure 6.20 10‐year‐old feline influenza virus–positive cat with subcutaneou...
Figure 6.21 Outdoor cat with firm swelling and multiple draining tracts on a...
Figure 6.22 Dog with a large, firm mass on the side of the muzzle, draining ...
Chapter 7
Figure 7.1
Sarcoptes scabiei
. Round to oval mite with four short legs, termi...
Figure 7.2 Chronic case of scabies. Entire pinnae affected. The pinnae are t...
Figure 7.3 Dog with scabies. Generalized papular eruption with excoriations....
Figure 7.4 Dorsum of dog in Figure 7.3: more profound excoriations with papu...
Figure 7.5
Scabies scabiei
on skin scraping.
Figure 7.6
Notoedres cati
. A round mite with four short forelimb legs with m...
Figure 7.7 Cat with
Notoedres cati
. Severe crusting and excoriation of the h...
Figure 7.8 Canine demodex. Current consensus is that
Demodex cornei
is not a...
Figure 7.9 Varies clinical presentations of canine demodicosis.
Figure 7.10 Papules, pustules, and comedones associated with demodicosis.
Figure 7.11 Erythema with severe follicular plugging.
Figure 7.12 Dog with furunculosis secondary to demodicosis.
Figure 7.13 Hair pluck with demodex.
Figure 7.14 Feline leukemia‐positive cat with
Demodex cati
. Severe crusting ...
Figure 7.15 Diabetic cat with
Demodex cati
. Generalized alopecia, fine crust...
Figure 7.16
Demodex gatoi
infections. Notice the alopecia on the ventrum and...
Figure 7.17
Felicola subrostratus
.
Figure 7.18 Cat with nits. White arrows designate nits.
Chapter 8
Figure 8.1 Cutaneous manifestations of leishmaniasis in dogs. (a). Facial ex...
Figure 8.2 (a) Perioral ulcerative lesions in a cat with sporotrichosis. (b)...
Chapter 9
Figure 9.1 Chronic flea‐allergic dog. Pruritus has focused on the sides and ...
Figure 9.2 Acute‐onset contact allergy in the inguinal area. Note the erythe...
Figure 9.3 Hives secondary to food allergy. Note the multiple hives coalesci...
Figure 9.4 Fore paw of an atopic dog. Note the mild erythema and lichenifica...
Figure 9.5 Typical atopic dermatitis presentation. Note the erythema periocu...
Figure 9.6 Chronic food‐allergic dog. Note the severe papular eruption on th...
Figure 9.7 Acute food‐allergic dog. Note the hair loss from the chest back w...
Figure 9.8 Milder case of contact allergy with secondary pyoderma. Note the ...
Figure 9.9 Papules on the pinnae of a patient allergic to plants.
Figure 9.10 Contact allergy in the patient in Figure 9.9. Note the erythema ...
Figure 9.11 Example of Commelina plant growing on a sidewalk. This is a grou...
Figure 9.12 Example of a positive patch test. Note the erythema and papules ...
Chapter 10
Figure 10.1 Alopecia secondary to flea allergy: note that the underlying ski...
Figure 10.2 Pruritus visual analog scale for a cat.
Figure 10.3 Cat with excoriations, alopecia and erosions in the inguinal are...
Figure 10.4 Miliary dermatitis in a cat secondary to feline atopic skin synd...
Figure 10.5 Indolent ulcer secondary to flea allergy: note the large, erosiv...
Figure 10.6 Multiple eosinophilic plaques on the ventrum of a cat secondary ...
Figure 10.7 Diagnosis flow chart for feline hypersensitivity.
Figure 10.8 Mosquito hypersensitivity: note the multiple small erosions on t...
Figure 10.9 Intradermal skin test: note the positive wheal‐and‐flare reactio...
Figure 10.10 View of feline intradermal allergy test with Wood’s lamp after ...
Chapter 11
Figure 11.1 Cytology of pemphigus pustule. White arrows indicate acantholyti...
Figure 11.2 Clinical features of canine pemphigus foliaceus. Note the pustul...
Figure 11.3 Severe hyperkeratosis secondary to pemphigus foliaceus.
Figure 11.4 Subcorneal pustules of pemphigus foliaceus.
Figure 11.5 Clinical features of feline pemphigus foliaceus. Note the small ...
Figure 11.6 Large pemphigus foliaceus collarettes with crusting and pustules...
Figure 11.7 Sebaceous adenitis. Change in coat color and character.
Figure 11.8 Sebaceous adenitis.
Figure 11.9 Idiopathic sterile nodular panniculitis. (a and c) Nodular lesio...
Figure 11.10 Idiopathic sterile nodular panniculitis. Healed lesion with atr...
Figure 11.11 Symmetric lupoid onychodystrophy.
Figure 11.12 Proliferative thrombovascular necrosis of the pinnae. (a) Scall...
Figure 11.13 Proliferative thrombovascular necrosis (PTN) of the pinnae. (a)...
Figure 11.14 Generalized vasculitis lesions. Note the paws, which are swolle...
Figure 11.15 Vasculitis lesions. (a) Black circles indicate areas of erythem...
Figure 11.16 Clinical variations of discoid lupus erythematosus. Note the de...
Figure 11.17 Mucocutaneous lupus erythematosus. Note nose erythema and ulcer...
Figure 11.18 Erythema multiforme. The edges of the erosions and the collaret...
Figure 11.19 German shepherd pyoderma. Note the multiple crust and erosive l...
Figure 11.20 Vesicular cutaneous lupus erythematosus. Note the multiple ulce...
Figure 11.21 Exfoliative cutaneous lupus erythematosus. Note the fine scale ...
Figure 11.22 Active ischemic dermatopathy lesions. Note the alopecia and cru...
Figure 11.23 Healed ischemic dermatopathy lesions. Note the scarring with hy...
Chapter 12
Figure 12.1 Hypothyroidism. Note the thin, brittle hair coat.
Figure 12.2 Hypothyroidism with secondary
Malassezia
and bacterial dermatiti...
Figure 12.3 Severe otitis externa due to hypothyroidism in a dog: proliferat...
Figure 12.4 Acral lick granuloma secondary to hypothyroidism in a 4‐year‐old...
Figure 12.5 Dog with demodicosis secondary to hypothyroidism. Note the alope...
Figure 12.6 Hyperadrenocorticism in a dog. Note the pot‐bellied appearance a...
Figure 12.7 Hyperadrenocorticism in a dog. Note the generalized alopecia and...
Figure 12.8 Calcinosis cutis in a dog. The lesion is made up of multiple fir...
Figure 12.10 Dog with Cushing’s disease, calcinosis cutis, and deep pyoderma...
Figure 12.11 Thin skin in a cat with hypercortisolism.
Figure 12.12 Hepatocutaneous syndrome. Note the diffuse crusting and fissuri...
Figure 12.13 Hepatocutaneous syndrome. Diffuse, thick, adherent crusts with ...
Figure 12.14 Hepatocutaneous syndrome: erythema and erosion of the genital r...
Figure 12.15 Hepatocutaneous syndrome: erosion of the prepuce.
Figure 12.16 Zinc‐responsive dermatosis in a husky: crusting and alopecia.
Figure 12.18 Zinc‐responsive dermatosis. Closeup view of the gray/white, dry...
Figure 12.19 Alopecia X. Note truncal alopecia that spares the head.
Figure 12.20 Alopecia X. Note the loss of secondary hairs.
Chapter 13
Figure 13.1 Examples of types of otitis. Acute otitis: the pinna and vertica...
Figure 13.2 Examples of chronic otitis cases that would benefit from the ant...
Figure 13.3 Normal tympanic membrane. The malleus is the small C‐shaped bone...
Figure 13.4 Examples of otitis media. Ruptured
tympanic membrane
) has a gre...
Figure 13.5 Where to perform a myringotomy. The blue circle indicates the ca...
Figure 13.6 Removal of mucus from the middle ear. The first picture shows a ...
Figure 13.7 View of the bulla through a video‐otoscope. In the mildly inflam...
Chapter 15
Figure 15.1 Keratolytic agents. These agents promote the decrease of adhesio...
Figure 15.2 Keratoplastic agents. These agents attempt to normalize keratini...
Figure 15.3 Localized Cushing’s disease secondary to topical steroids. This ...
Figure 15.4 Clinical conditions that can benefit from antiseborrheic agents....
Figure 15.5 Emollients/occlusives. Emollients are oily substances that fill ...
Figure 15.6 Humectants. Humectants are hygroscopic substances that attract w...
Chapter 16
Figure 16.1 Antibiotics’ mechanisms of action (green arrows) and bacterial m...
Chapter 17
Figure 17.1 Omega‐3 and omega‐6 polyunsaturated fatty acid desaturation and ...
Figure 17.2 Alpha‐linolenic acid metabolism. Acetyl Co.‐A, acetyl coenzyme A...
Figure 17.3 Representation of the cell membrane phospholipid bilayer. (a) In...
Chapter 18
Figure 18.1 Genomic effect of glucocorticoids (GC). GC passively diffuse thr...
Figure 18.2 Calcinosis cutis plaque on a dog’s abdomen secondary to oral pre...
Figure 18.3 Localized iatrogenic hyperadrenocorticism secondary to topical b...
Figure 18.4 Multiple full‐thickness skin tears on a cat’s dorsal neck and ba...
Figure 18.5 Mechanism of action of lokivetmab and oclacitinib. (a) Oclacitin...
Figure 18.6 Cyclosporine’s mechanism of action. Cyclosporine (CsA) binds wit...
Figure 18.7 Severe gingival hyperplasia in the mouth of a dog secondary to l...
Figure 18.8 Papillomas in the mouth of a dog secondary to long‐term cyclospo...
Chapter 20
Figure 20.1 Formation of monoclonal antibodies: red, mouse antibody; green, ...
Figure 20.2 DNA vaccination. Antigens (proteins) are linked to the
virus‐lik
...
Figure 20.3 Explanation of the Janus kinase/signal transducer and activator ...
Chapter 21
Figure 21.1 Some of the tips commonly used with the CO
2
laser. From top to b...
Figure 21.2 Meibomian gland adenoma on the lower eyelid of a dog. Left image...
Figure 21.3 Long rigid tip is advanced through the working channel of the Me...
Figure 21.4 Pre laser: ceruminous gland cystomatosis occluding the external ...
Figure 21.5 Ceruminous gland cystomatosis in the vertical external ear canal...
Figure 21.6 Ceruminous gland adenoma that is completely occluding the ear ca...
Figure 21.7 Footpad papillomas that were causing significant discomfort. The...
Figure 21.8 Oral papillomatosis in a young dog. Unfortunately, the papilloma...
Figure 21.9 Interdigital cysts on the palmar aspect of this dog’s paw with a...
Figure 21.10 Paintbrush tip for CO
2
with the end visible.
Figure 21.11 Cross‐section of the excised interdigital cystic tissue. Note t...
Chapter 24
Figure 24.1 Dermatologic patient history form.
Figure 24.2 Pruritus scale.
Figure 24.3 Severe cocci on ear cytology (100×).
Figure 24.4 Severe rods and neutrophils on ear cytology (100×).
Figure 24.5 Demodex mite counting sheet.
Figure 24.6
Demodex canis
(blue arrows) and a few short fat canine demodex (...
Figure 24.7
Microsporum canis
colonies on a dermatophyte test medium plate. ...
Figure 24.8
Microsporum gypseum
macroconidia. Note that the macroconidia hav...
Figure 24.9 Direct impression cytology from a crusted area.
Figure 24.10 Opening a pustule to apply a slide directly for cytology. Note ...
Figure 24.11 Purulent material collected on the needle being spread on a sli...
Figure 24.12 Neutrophils and cocci on acetate tape preparation (100×).
Figure 24.13 Eosinophils on acetate tape preparation (100×).
Chapter 25
Figure 25.1 Calgary‐Cambridge guide framework for communication.
Figure 25.2 When clients reach the tipping point of frustration, there are n...
Figure 25.3 Barriers to referral, as indicated by primary care veterinarians...
Figure 25.4 Survival time of dogs treated for
congestive heart failure
(
CHF
)...
Figure 25.5 Relationships between
primary care veterinarians
(
pcDVMs
) and sp...
Figure 25.6 Top reasons pet owners accept a referral recommendation.
Guide
Cover Page
Title Page
Copyright Page
Acknowledgments
Foreword
List of Contributors
Table of Contents
Begin Reading
Index
Wiley End User License Agreement
Pages
iii
iv
vii
vii
vii
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
66
67
68
69
70
71
72
73
74
75
76
77
78
79
80
81
82
83
84
85
86
87
88
89
90
91
92
93
94
95
96
97
98
99
100
101
102
103
104
105
106
107
108
109
110
111
112
113
114
115
116
117
118
119
120
121
122
123
124
125
126
127
128
129
130
131
132
133
134
135
136
137
138
139
140
141
142
143
144
145
146
147
148
149
150
151
152
153
154
155
156
157
158
159
160
161
162
163
164
165
166
167
168
169
170
171
172
173
174
175
176
177
178
179
180
181
182
183
184
185
186
187
188
189
190
191
192
193
194
195
196
197
198
199
200
201
202
203
204
205
206
207
208
209
210
211
212
213
214
215
216
217
218
219
220
221
222
223
224
225
226
227
228
229
230
231
232
233
234
235
236
237
238
239
240
241
242
243
244
245
246
247
248
249
250
251
252
253
254
255
256
257
Diagnostics and Therapy in Veterinary Dermatology
Edited by
Dawn Logas
Veterinary Dermatology Center
Silver Springs, FL, USA
This edition first published 2022© 2022 John Wiley & Sons, Inc.
All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, except as permitted by law. Advice on how to obtain permission to reuse material from this title is available at http://www.wiley.com/go/permissions.
The right of Dawn Logas to be identified as the author of the editorial material in this work has been asserted in accordance with law.
Registered OfficeJohn Wiley & Sons, Inc., 111 River Street, Hoboken, NJ 07030, USA
Editorial Office111 River Street, Hoboken, NJ 07030, USA
For details of our global editorial offices, customer services, and more information about Wiley products visit us at www.wiley.com.
Wiley also publishes its books in a variety of electronic formats and by print‐on‐demand. Some content that appears in standard print versions of this book may not be available in other formats.
Limit of Liability/Disclaimer of WarrantyThe contents of this work are intended to further general scientific research, understanding, and discussion only and are not intended and should not be relied upon as recommending or promoting scientific method, diagnosis, or treatment by physicians for any particular patient. In view of ongoing research, equipment modifications, changes in governmental regulations, and the constant flow of information relating to the use of medicines, equipment, and devices, the reader is urged to review and evaluate the information provided in the package insert or instructions for each medicine, equipment, or device for, among other things, any changes in the instructions or indication of usage and for added warnings and precautions. While the publisher and authors have used their best efforts in preparing this work, they make no representations or warranties with respect to the accuracy or completeness of the contents of this work and specifically disclaim all warranties, including without limitation any implied warranties of merchantability or fitness for a particular purpose. No warranty may be created or extended by sales representatives, written sales materials or promotional statements for this work. The fact that an organization, website, or product is referred to in this work as a citation and/or potential source of further information does not mean that the publisher and authors endorse the information or services the organization, website, or product may provide or recommendations it may make. This work is sold with the understanding that the publisher is not engaged in rendering professional services. The advice and strategies contained herein may not be suitable for your situation. You should consult with a specialist where appropriate. Further, readers should be aware that websites listed in this work may have changed or disappeared between when this work was written and when it is read. Neither the publisher nor authors shall be liable for any loss of profit or any other commercial damages, including but not limited to special, incidental, consequential, or other damages.
Library of Congress Cataloging‐in‐Publication Data
Names: Logas, Dawn, editor.Title: Diagnostics and therapy in veterinary dermatology / edited by Dawn Logas.Description: First edition. | Hoboken, NJ : Wiley‐Blackwell, [2022] | Includes bibliographical references and index.Identifiers: LCCN 2021043862 (print) | LCCN 2021043863 (ebook) | ISBN 9781119680604 (hardback) | ISBN 9781119680628 (adobe pdf) | ISBN 9781119680635 (epub)Subjects: MESH: Skin Diseases–veterinary | Skin ManifestationsClassification: LCC SF901 (print) | LCC SF901 (ebook) | NLM SF 901 | DDC 636.089/65–dc23LC record available at https://lccn.loc.gov/2021043862LC ebook record available at https://lccn.loc.gov/2021043863
Cover Design: WileyCover Image: © Dawn Logas
Acknowledgments
First, I want to thank Gail Kunkle and Richard Halliwell for their support and mentorship that got me started in dermatology. Second, I want to thank my clients and patients over the last 35 years who have taught me so much about dermatology that I did not know before. Next, I want to thank my husband, Paul, and sons, Christopher and Jacob, for all their love and support over the years. I love you guys more than you will ever know. Finally, I want to thank my best friend and business partner, Marcia Schwassmann, for making me a better person and veterinarian along with helping me edit this book.
Dawn Logas
Foreword
Dear Colleague
This book is not meant to be an all‐inclusive dermatology text. It is meant to help you understand how dermatologists think and what we feel is important when working up our cases, so you can improve how you work up your own dermatology cases. It will also hopefully improve the use of our veterinary nurses and the communication between the primary care veterinarian and the dermatologist. Furthermore, I have included information in this book about diseases whose incidences are increasing because of climate change and issues such as antibiotic resistance, which are not found in other currently available dermatology texts. As veterinarians we will become more important in the One Health movement as infectious diseases spread to new areas and antibiotic resistance continues to spread.
I want to thank the authors who contributed to this book for their hard work and diligence in delivering practical chapters with information that primary care veterinarians can use every day.
Dawn Logas
List of Contributors
Joseph M. Blondeau, BSc, MSc, PhDRoyal University Hospital and University of Saskatchewan, Saskatoon, Saskatchewan, Canada
Leah D. Blondeau, PhDRoyal University Hospital and University of Saskatchewan, Saskatoon, Saskatchewan, Canada
Megan Boyd, DVM, DACVDAnimal Dermatology Center, Studio City, CA, USA
Ceara Byrne, MS CS Georgia Tech, PhDGeorgia Institute of Technology School of Interactive Computing, Atlanta, GA, USA
Christine L. Cain, DVM, DACVDSchool of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA
Ana Milena Carmona‐Gil, DVM, MScDermaVet Centro de Dermatología Veterinaria, Medellín, Antioquia, Colombia
Catlin Contreary, DVM, DACVDVeterinary Dermatology Center, Maitland, FL, USA
Katherine Doerr, DVM, DACVDVeterinary Dermatology Center, Maitland, FL, USA
Valerie Fadok, DVM, DACVD, PhDZoetis, Bellaire, TX, USA
Cecilia Friberg, DVM, DACVDSodra Djursjukhuset, Stockholm, Sweden
Natalie Gedon, DVMUniversity of North Carolina College of Veterinary Medicine, Raleigh, NC, USA
Darcie Kunder, VMD, DACVDFriendship Hospital for Animals, Washington, DC, USA
Judy Lethbridge, RVT (registered veterinary technician)Veterinary Dermatology Center, Maitland, FL, USA
Dawn Logas, DVM, DACVDVeterinary Dermatology Center, Maitland, FL, USA
Jacob Logas, MS CS Georgia Tech, PhDGeorgia Institute of Technology School of Interactive Computing, Atlanta, GA, USA
Rosanna Marsella, DVM, DACVDUniversity of Florida, Gainesville, FL, USA
Ralf Mueller, DVM, MANZCVSc (Canine Medicine), DACVD, FANZCVSc (Dermatology), DECVDCentre for Clinical Veterinary Medicine, LMU Munich, Germany
Luisito S. Pablo, DVM, MS, DACVAACollege of Veterinary Medicine, University of Florida, Gainesville, FL, USA
Mark G. Papich, DVMNorth Carolina State University, Raleigh, NC, USA
Jason B. Pieper, DVM, MS, DACVDIowa State University, Ames, IA, USA
Domenico Santoro, DVM, MS, DrSc, PhD, DACVD, DECVD, DACVM (Bacteriology, Mycology, Immunology)University of Florida, Gainesville, FL, USA
JoAnn Stewart, RVT, CVPM, CCFPExecutive Director, Collaborative Care Coalition, Gurnee, IL, USA
Rebekah Westermeyer, BSEd, DVM, DACVD, MRCVSAnimal Allergy Specialists, Oahu, HI, USAAsia Veterinary Diagnostics, Kowloon, Hong Kong
Amelia White, DVM, MS, DACVDAuburn University College of Veterinary Medicine, Auburn, AL, USA
Michelle Woodward O’Gorman, DVM, DACVDBaton Rouge Veterinary Specialists, Baton Rouge, LA, USA
1 The Skin as an Immune Organ
Domenico Santoro and Megan Boyd
KEY POINTS
The skin is an extremely active immunologic organ.
The skin has many resident immunologically active cells.
The skin defense system includes a physical barrier (stratum corneum and hair), a chemical barrier (fatty acids and antimicrobial peptides), an immunologic barrier (innate and adaptive immune system), and a microbiological barrier (beneficial microorganisms).
Keratinocytes are the most immunologically active cells in the epidermis.
The skin is commonly affected by immune system disorders.
The skin is the largest organ in the body. It has long been known as the primary physical barrier between an organism and its environment, but since the early 1980s the skin has been recognized as an active immune organ with its own skin‐associated immune system. The skin’s defense system consists of physical, chemical, immunologic, and microbiologic components that protect the body against trauma, chemicals, toxins, and microorganisms.
The physical barrier represents the first line of defense against invaders. It is composed of keratinocytes tightly bonded together by a lipid‐rich mortar in the stratum corneum (top layers) and keratinocytes joined together by tight cell‐to‐cell junctions in the lower layers. The chemical barrier consists of compounds with active antimicrobial activity, including fatty acids and antimicrobial or host defense peptides secreted by sebaceous glands and keratinocytes. If the physical and chemical defenses of the skin are overcome by invaders, components of the innate and active immune system along with beneficial microorganisms in the skin microbiome become important. Beneficial microorganisms compete for the same niche as pathogens and actively secrete antimicrobial peptides (AMPs) that inhibit the proliferation of pathogenic competitors.
When pathogenic microorganisms breach the physical and chemical defenses of the skin, they activate the skin‐associated lymphoid tissue (SALT) (Table 1.1). SALT includes dendritic cells, mast cells, lymphocytes, and keratinocytes, and forms part of the innate immune system (Figure 1.1). Innate immunity, which is considered the most ancient branch of the body’s immune defenses, is characterized by a rapid onset of action (minutes to hours), a lack of specificity (it recognizes common microbial structures as opposed to specific organisms), and a lack of memory, which means the response does not improve with each exposure. Cells of the innate immune system include macrophages, dendritic cells, neutrophils, natural killer (NK) cells, mast cells, and keratinocytes. When innate immunity is overwhelmed, the adaptive branch of the immune system (Figure 1.2), primarily made of T and B lymphocytes, is activated. The adaptive immune response is characterized by a slow onset of action (days to weeks), high specificity (recognizes unique antigens), and memory, which means the speed and magnitude of the response improve with each exposure. The innate and adaptive branches of the immune system are highly interconnected. When cells of the innate immune system are activated, they secrete numerous inflammatory cytokines and chemokines that prime and direct the adaptive immune system’s response.
Table 1.1 Cells of the innate and adaptive immune system discussed in this chapter.
Cell type
Functions
Location
Cytokines produced
Expressed molecules
Innate
Keratinocyte
Mechanical barrier, epidermal production Immune function
Epidermis
IL‐1, IL‐6, TNF, IL‐8, IL‐10, IL‐12, IL‐15, IL‐18, IL‐19, IL‐20, TGF, IL‐20, IL‐23, GM‐CSF, G‐CSF
TLR, MHC‐I, MHC‐II, AMP
Langerhans cell
Antigen‐presenting cell
Epidermis
IL‐12, IL‐23, IL‐6, TNF
Fc and mannose receptors, ICAM‐1, IL‐12, MHC‐II
Dermal dendritic cell
Antigen‐presenting cell
Dermis
IL‐12, IL‐23, IL‐6, TNF
Fc and mannose receptors, ICAM‐1, IL‐12, MHC‐II
Mast cell
Hypersensitivity reactions, vasodilation, chemotaxis, inflammation
Dermis
TNF, IL‐1, IL‐4, IL‐5, IL‐6, IL‐13, CCL3, CCL4, IL‐3, GM‐CSF
TLRs, NF‐kB, NFAT, AP‐1
Eosinophil
Hypersensitivity reactions, vasodilation, chemotaxis, inflammation
Dermis
IL‐3, IL‐5, IL‐8, IL‐10, leukotrienes, GM‐CSF, hydrolases
Fc receptor
Neutrophil
Innate immunity, phagocytosis
Dermis
ROS, proteolytic enzymes
TLRs, lectin receptor, mannose receptor
M1 macrophage
Phagocytosis, antigen presentation, bactericidal activity
Dermis
IL‐6, IL‐12, TNF, iNOS
JAK1, JAK2, STAT1, STAT2
M2 macrophage
Phagocytosis, antigen presentation, regenerative effects
Dermis
IL‐10, TGF, arginase‐1
JAK1, JAK2, JAK3, STAT6
ILC (Innate lymphoid cell)
Innate immunity
Dermis
IL‐1, IL‐23, IL‐25, IL‐33, TSLP
Id2, T‐bet, GATA 3, ROR
Both innate and adaptive
γ/δ T cell
Elimination of intracellular microorganisms and infected cells; cell death
Dermis
IL‐17, IFN
MHC‐ I
Natural killer cell
Innate immunity against viruses and intracellular bacteria
Dermis
IFN, GM‐CSF, IL‐3
MHC‐I
Natural killer T cell
Elimination of lipid antigens
Dermis
IL‐4, IL‐17, IL‐22, IFN
MHC‐1
Adaptive
B lymphocyte
Humoral response
Dermis
IL‐2, IL‐4, IL‐6, IL‐11, IL‐13, TNF, BAFF
Antibodies
T‐helper lymphocyte
Coordinates immune function
Dermis
Various depending on the type of T‐helper cell
Various depending on the type of T‐helper cell
T‐cytotoxic lymphocyte
Elimination of intracellular microorganisms and infected cells
Dermis
IFN
Perforin, granzyme, granulysin
T‐regulatory lymphocytes
Control of immune response
Dermis
IL‐10, TGF
FoxP3, STAT5
Key: AMP, antimicrobial peptides; AP, activator protein; BAFF, B‐cell activating factor; CCL, chemokine ligand; FoxP3, forkhead box P3 protein; GATA, transcription factor; G‐CSF, granulocyte colony‐stimulating factor; GM‐CSF, granulocyte macrophage colony‐stimulating factor; ICAM, intercellular adhesion molecule; Id2, DNA binding protein inhibitor 2; IFN, interferon; IL, interleukin; iNOS, inducible nitric oxide synthase; JAK, Janus kinase; MHC, major histocompatibility complex; NFAT, nuclear factor of activated T cell; NF‐kB, nuclear factor kappa B; ROR, retinoic acid‐related orphan receptors; ROS, reactive oxygen species; STAT, signal transducer and activator of transcription; T‐bet, T box transcription factor; TGF, transforming growth factor; TLR, Toll‐like receptor; TNF, tumor necrosis factor; TSLP, thymic stromal lymphopoietin.
Figure 1.1 Innate skin immune system. 1. The innate immune system is activated when damage‐associated molecular pattern (DAMP) molecules released by damaged cells or pathogen‐associated molecular pattern (PAMP) molecules on pathogens are recognized by pattern‐recognition receptors such as Toll‐like receptors on both dendritic cells (Langerhans cells) and keratinocytes. 2. This leads to the activation of keratinocytes directly and the release of cytokines by the Langerhans cells that also activate the keratinocytes. 3. The activated keratinocyte releases various cytokines and AMPs to directly destroy the invading pathogen. 4. Neutrophils and macrophages are recruited to directly destroy the invaders. IFN, interferon; IL, interleukin; TNF, tumor necrosis factor.
Immune System of the Skin
The skin is a complex organ composed of an outermost layer, the epidermis; a middle layer, the dermis and cutaneous appendages; and an inner layer, the subcutis. Immune cells and inflammatory mediators are active in all these layers. It is important to understand that immune cells and inflammatory mediators are extremely interconnected and work in concert, as opposed to having isolated effects. If we compare the two branches of the immune system to an army, the innate immune system would be the entrenched peacekeeping force while the adaptive immune system would be the cavalry called in as reinforcements. By constantly communicating via cytokines and chemokines, they work together as one system to protect the host.
Epidermis
The major physical defense of the skin is the stratum corneum. This outermost layer continuously sheds into the environment, taking pathogens along with it. In addition to keratinocyte exfoliation, compounds present in the intercellular lipid cement create an environment unfavorable to pathogen invasion. These compounds include sodium chloride, albumin, complement components, transferrin, interferons, lipids, and antibodies donated by the adaptive immune system.
Below the stratum corneum the living epidermis is composed mainly of keratinocytes that are bound together by various junctional structures, including desmosomes, hemidesmosomes, and tight junctions. In addition to forming the major structural component of the epidermis, keratinocytes are many times the first to detect pathogens. By initiating the immune response, they act as sentinel cells for both the innate and adaptive immune systems. Keratinocytes produce small quantities of AMPs on a regular basis. AMPs are small cationic molecules that are a first line of defense against pathogens. They block lipopolysaccharides (a major negatively charged component of the outer membrane of gram‐negative bacteria), directly kill microbes, and induce histamine release from mast cells. Keratinocytes also detect highly conserved microbial surface structures (e.g. lipopolysaccharides, flagellins, teichoic acids) called pathogen‐associated molecular pattern (PAMP) molecules via pattern‐recognition receptors such as Toll‐like receptors. Other pattern‐recognition receptors on the keratinocyte surface detect damage‐associated molecular pattern molecules (DAMP) that are endogenous ligands/markers produced by injured or dying host tissue. These are important in the detection of irritants and toxins. Once pattern‐recognition receptors are triggered, the keratinocyte is activated. Depending on the type of assault and which pattern‐recognition receptors are triggered, the activated keratinocyte then produces more AMPs, and various pro‐inflammatory cytokines (a large group of small molecules important in cell signaling). Some of these cytokines have immediate effects on the invaders (innate response) that directly neutralize the pathogen, while others are important in recruiting and activating B and T lymphocytes (adaptive response). Once activated, keratinocytes express a wider variety of pattern‐recognition receptors. Keratinocytes can also act as antigen‐presenting cells for the adaptive immune response. They can express both major histocompatibility complex molecules (MHC) I and II on their surface. They are not able to prime naïve T cells, but can present antigen to both T‐helper (CD4+) and cytotoxic (CD8+) T lymphocytes.
Figure 1.2 Adaptive skin immune system. 1. Langerhans cells (LCs) are activated once they uptake and process the antigen. 2. Some will mature and migrate along with some activated dermal dendritic (DD) cells to the local lymph node. 3. The antigen in association with major histocompatibility complex (MHC) I or II will prime naïve T and B cells. 4. The primed T‐helper (CD4+) and cytotoxic cells (CD8+) enter the blood system and return to the area of inflammation along with other inflammatory cells via adhesion molecules like intercellular adhesion molecule (ICAM)‐1 and vascular cell adhesion molecule (VCAM)‐1. 5. The primed T lymphocytes mature into various types of T‐helper (Th) cells, depending on which cytokines are produced by keratinocytes and dendritic cells. These mature T‐helper cells are responsible for amplifying the inflammatory response. 6. Primed T‐helper cells are also able to prime B cells in the skin that are displaying the same antigen in association with MHC on the B cell’s surface. The B cell will then mature into plasma cell and produce immunoglobulins against that antigen. CF, chorion factor; IFN, interferon; IL, interleukin; M, macrophage; NK, natural killer cell; NO, nitric oxide; TGF, transforming growth factor; TNF, tumor necrosis factor.
Melanocytes and Langerhans cells are the other major immunologically active cell types in the epidermis. Melanocytes’ major function is the production of melanin to protect keratinocytes from the harmful effects of ultraviolet radiation (UVR). However, they also play an important regulatory role in both the innate and adaptive immune systems by promoting phagocytosis and producing a series of pro‐inflammatory cytokines. Like keratinocytes, they can also express various pattern‐recognition receptors such as Toll‐like receptors.
Langerhans cells and dermal dendritic cells are the most important antigen‐presenting cells in the skin, as they are the only cells able to activate naïve T lymphocytes. Depending on the microenvironment and the immunologic triggers present, Langerhans cells can mediate a tolerogenic response through the production of interleukin 10 (IL‐10), or they can promote an inflammatory response. Once in contact with an invader, Langerhans cells phagocytose the antigen, process it, and represent it on their surface in association with MHC‐II. This causes the maturation of the Langerhans cells, which then migrate to the regional lymph node to prime naïve T lymphocytes.
The epidermis also hosts resident memory T lymphocytes, part of the adaptive immune system. These cutaneous memory T lymphocytes may possess either α/β or γ/δ T‐cell receptors. Those with γ/δ receptors are considered a hybrid between an innate and an adaptive immune cell. They bind to common PAMP molecules or respond to the class Ib MHC molecules produced by stressed, cancer‐, or virus‐infected cells.
Dermis
The dermis is mainly composed of extracellular matrix proteins that provide structure and elasticity to the skin. It is separated from the epidermis by the basal membrane, a thin layer of extracellular matrix proteins. This membrane regulates the movement of cells and substances from the dermis to the epidermis and anchors the basal epidermal keratinocytes to the dermis via hemidesmosomes. The dermis contains hair follicles, glandular structures, specialized neural receptors, as well as blood and lymphatic vessels essential for the support and maintenance of dermal and epidermal cells.
Fibroblasts are the most abundant immunologically active cells in the dermis. Their primary function is production of the extracellular matrix that provides structural support for the dermis and a scaffolding that allows cells of the immune system to move easily through the dermis. Fibroblasts secrete a variety of cytokines, including chemoattractants for T lymphocytes, and direct the inflammatory response that is part of wound healing. Fibroblasts produce matrix metalloproteinases, a group of enzymes responsible for the degradation of the extracellular matrix, but they also produce tissue inhibitors of matrix metalloproteinases. Therefore, fibroblasts facilitate both activation and termination of inflammation.
Endothelial cells and neurons are also essential for the dermal immune response. Endothelial cells regulate the influx of inflammatory cells from the blood into the dermis through the activation of adhesion molecules and cytokines. During the initial phase of inflammation, endothelial cells activate multiple Toll‐like receptors and various adhesion molecules, including intercellular adhesion molecule‐1 (ICAM‐1), vascular cell adhesion molecule‐1 (VCAM‐1), and selectins E and P. As the inflammatory response progresses, endothelial cells secrete more pro‐inflammatory cytokines such as IL‐1, tumor necrosis factor alpha (TNF‐α), and interferon gamma (IFN‐γ), which in turn increase the expression of adhesion molecules to further facilitate leukocyte migration and extravasation.
Nerves are important for sensation and they also have an intimate connection with memory T cells. Neurons modulate signals between the innate and adaptive branches of the immune system by producing substance‐P, calcitonin gene‐related peptide, and alpha melanocyte‐stimulating hormone. These substances support a healthy level of inflammation and help to resolve the inflammatory response when needed.
The dermis is home to other cells of the innate immune system (granulocytes, NK cells, dendritic cells, macrophages) and lymphocytes (adaptive immune system cells). Neutrophils and macrophages are part of the first line of defense against microorganisms. As soon as an invader is detected, these cells are called to the site of infection by potent chemoattractants. Once there, they express receptors that recognize, bind, capture, and phagocytose microorganisms. Neutrophils are also able to externally project their DNA and DNA‐associated proteins to form “sticky” neutrophil extracellular traps (NETs) that trap pathogens like flies on a spider’s web.
Macrophages are a bridge between the innate and adaptive arms of the immune system. In addition to phagocytosing microorganisms, macrophages remove debris, dead cells, and exogenous or endogenous inflammatory stimuli (e.g. free melanin or keratin). They also act as antigen‐presenting cells. Macrophages can recognize, bind, capture, and destroy microorganisms directly or via their recognition of antibody molecules, complement proteins, or lectins. Macrophages secrete various cytokines that direct the immune response. Different types of macrophages have recently been identified: M0, M1, M2, M4, M17, and Mreg. M1 macrophages secrete TNF‐α, IL‐6, and IL‐12, cytokines that promote a T‐helper type 1 pro‐inflammatory immune response. M2 macrophages promote an anti‐inflammatory immune response through the secretion of IL‐10 and IL‐4. M4 macrophages secrete TNF‐α, IL‐6, matrix metalloproteinases 7 and 12, and macrosialin, all of which reduce phagocytosis and induce a pro‐inflammatory immune response. Finally, M17 and Mreg cells have been proposed, but their characterization and involvement in the inflammatory process need further clarification.
Eosinophils are more abundant in the later stages of inflammation. They are important in the pathogenesis of allergic and parasitic diseases, both driven by T‐helper type 2 cytokines. Once eosinophils reach the site of inflammation, they release granular proteins highly toxic to parasites. Eosinophils are also essential in secreting cytokines characteristic of an allergic response. Finally, eosinophils release prostaglandins and leukotrienes that cause vasodilation and chemotaxis of neutrophils and prolong an allergic response. Eosinophils have a very strong connection with mast cells, mononuclear granulocytes essential for the allergic response and wound healing.
Mast cells in the skin are highly associated with blood vessels and have both immunoglobulin (Ig) E and complement receptors on their surface. Upon activation, mast cells release a variety of vasoactive and pro‐inflammatory substances, including histamine, serotonin, proteases, leukotrienes, prostaglandins, and cytokines. Along with pro‐inflammatory mediators, mast cells also secrete large quantities of transforming growth factor beta (TGF‐β), platelet‐derived growth factor (PDGF), and fibroblast growth factors (FGFs), all of which are essential mediators of tissue repair.
NK cells and dendritic cells represent the other innate immune cells present in the dermis. NK cells are lymphocytes that express neither T‐ nor B‐cell receptors. Until recently, they were thought to belong exclusively to the innate immune system because of their ability to recognize patterns more than specific antigens. However, more recent studies have shown that NK cells have memory, making them part of the adaptive immune system. Another peculiarity of NK cells is their ability to recognize MHC‐I on cell surfaces. This ability makes NK cells the major sentinel cells in the recognition of virally infected or cancerous cells. Finally, NK cells can bind IgG‐coated pathogens and cells (antibody‐dependent cellular cytotoxicity), leading to the release of cytotoxins (granzyme, granulysin, and perforin), which kill the infected cell. Another cell that has characteristics of both innate and adaptive immunity is the NK T cell, which is a hybrid between T cells and NK cells.
Dendritic cells are found in the dermis as well as the epidermis. They reside in the upper dermis just below the basal membrane. Dermal dendritic cells along with Langerhans cells in the epidermis are the major antigen‐presenting cells of the skin. They deliver processed antigen to lymph nodes to prime naïve T lymphocytes of the adaptive immune system. Once dermal dendritic cells are stimulated by antigen, they begin the maturation process, which involves a decrease in their phagocytic ability and an increase in expression of MHC‐II glycoproteins, increasing their antigen‐presenting function. Mature dermal dendritic cells are also able to redirect the local immune response through the secretion of inflammatory cytokines. In addition, they can express epithelial cell adhesion molecules and stimulate the transformation of B lymphocytes into plasma cells.
The dermis is also home to B and T lymphocytes, the major cells of the adaptive immune system. It has been estimated that the healthy dermis contains twice as many lymphocytes (~20 billion T cells) as there are in the blood. Most of these dermal lymphocytes are a heterogeneous population of T memory lymphocytes, including T‐helper (Th) type 1, 2, and 17, and T‐regulatory cells (Treg). More recently, Th3, 9, 22, and 25 lymphocytes have also been identified. These cells form an intricate network of resident adaptive immune cells ready to act in case of exposure to previously encountered antigens. They are mainly localized around capillaries, the dermoepidermal junction, and hair follicles and glands. Each one of these T‐cell subsets produces a specific pattern of cytokines. Th1 cells are mainly involved in fighting infection with intracellular microorganisms and secrete IFN‐γ, which activates macrophages. Th2 cells are mainly involved in fighting infections with extracellular microorganisms and allergies and secrete IL‐4 and IL‐13. Th17 cells are mainly involved in the inflammatory response against bacteria and fungi, and their role in atopic dermatitis and other cutaneous inflammatory diseases is being investigated. Th17 cells secrete IL‐17 and IL‐22. Th22 cells secrete only IL‐22, so are considered by some to be a subset of Th17 cells. Th22 cells are essential for keratinocyte proliferation and, like Th17 cells, are involved in atopic dermatitis and other inflammatory skin diseases. Treg cells secrete IL‐10 and TGF‐β. This subset of T lymphocytes is mainly involved in the suppression of the inflammatory response and plays a fundamental role in decreasing the immune response once the trigger has been eliminated. Alterations in the number of Treg cells and their characteristics have been associated with allergic and inflammatory skin diseases.
B lymphocytes are also found in the dermis, but in much lower numbers than T cells. B lymphocytes have multiple roles in the immune response besides producing antibodies once they have transformed into plasma cells. They express MHC‐II glycoproteins so they can present antigens, and they produce a variety of cytokines affecting both local and systemic immune responses. Recent evidence suggests that skin‐associated B cells may play a significant role in host defenses, regulation of microbes, and wound healing.
Subcutis
The subcutaneous tissue is mainly composed of fat and the primary cell type is the adipocyte. This tissue is highly innervated and vascularized. Historically, adipocytes’ only functions were thought to be energy storage, protection, and thermogenesis; however, new evidence suggests that adipocytes can play an important role in local and systemic immunity. Adipocytes express various innate immune receptors such as Toll‐like receptors and Nod‐like receptors. They can secrete inflammatory cytokines and can serve as antigen‐presenting cells for lymphocytes.
Defense from Harmful Substances
Acids, bases, free radicals, UVR, and natural or synthetic poisons are not always avoidable, thus the immune system is essential for protecting the host from these harmful substances. While it is intuitive that the innate immune system would protect against toxins and chemicals, both adaptive and immune responses are involved. Solar UVR causes formation of damaging free radicals. Natural moisturizing factors in the stratum corneum (specifically urocanic acid), keratinocyte DNA, and Langerhans cells all function as chromophores that absorb the UVR. When the UVR is absorbed, these cells produce TNF‐ α, IL‐10, and IL‐4 that encourage an adaptive immune response. TNF‐α and IL‐10 limit the recruitment of inflammatory cells to ensure an environment with just enough neutrophils and NK cells to eliminate any pathogens breaking through the temporarily damaged skin barrier.
Dysfunction of the Immune System
The immune system is a marvelous and extremely complex machine able to recognize and respond to an innumerable number of stimuli. Occasionally the system produces an excessive or inappropriate response to a stimulus, and this is the basis of hypersensitivity reactions.
Type I (Immediate) Hypersensitivity Reaction
Type I hypersensitivity is an acute inflammatory response to antigens (allergens) recognized by IgE receptors on tissue mast cells. Once the allergen cross‐links several IgE molecules, the mast cell degranulates, releasing inflammatory mediators into the surrounding tissue and causing acute inflammation. This type of hypersensitivity is typical of allergic reactions such as anaphylaxis.
Type II (Cytotoxic) Hypersensitivity Reaction
Type II hypersensitivity reactions are characterized by the presence of antibodies (mainly IgG) and complement proteins attached to host cells, which leads to the destruction of these cells. This type of hypersensitivity reaction is characteristic of autoimmune diseases. Medications, vaccinations, pathogens, toxins, and neoplasia can alter host cell morphology, thereby signaling that the cell is foreign rather than self; however, many autoimmune diseases occur without any known trigger. Pemphigus foliaceus is a common cutaneous autoimmune disease in which IgG antibodies are formed against desmosomal proteins, the attachment structures of keratinocytes.
Type III (Antigen–Antibody Complex) Hypersensitivity Reaction
Immune complexes are antigens bound to their antibodies. When excessive amounts of antigen are present in the body, more complexes than can be cleared efficiently by the body are formed. These complexes precipitate in tissue in large amounts and cause severe inflammation. The antigen–antibody complexes may remain at the initial site of attack or move through the bloodstream and lodge in distant locations such as capillaries or renal glomeruli. Once in the tissue, they trigger the accumulation of neutrophils, which release oxidants, inflammatory mediators, and enzymes that trigger additional inflammation and tissue damage. This type of hypersensitivity reaction is seen in many tick‐borne diseases and leishmaniasis, as well as autoimmune diseases such as systemic lupus erythematosus and vasculitis.
Type IV (Delayed or Cell‐Mediated) Hypersensitivity Reaction
Delayed hypersensitivity reactions involve Th lymphocytes, macrophages, and cytotoxic T lymphocytes. Delayed‐type hypersensitivities are induced by chronic intracellular infectious disease agents such as Mycobacteria spp. or Leishmania spp., as well as contact allergens. For dermatology, contact allergy is the perfect example of a type IV reaction. In contact allergic dermatitis, small molecules from plants or chemicals are absorbed into the skin. These molecules by themselves do not elicit a response from the immune system and are called haptens. Once these haptens attach to a host protein, this larger complex can then be recognized, processed, and presented as a complete antigen by Langerhans cells. During presentation to naïve T cells in the lymph node, the Langerhans cell releases cytokines that induce the formation of Th1 and Th17 cells. These cells then return to the skin and upon reexposure release Th1 cytokines and activate macrophages, causing the clinical signs associated with delayed hypersensitivity.
Recommended Reading
Eyerich, S., Eyerich, K., Traidl‐Hoffmann, C., and Biedermann, T. (2018). Cutaneous barriers and skin immunity: differentiating a connected network.
Trends Immunol.
39: 315.
Marshall, J.S., Warrington, R., Watson, W., and Kim, H.L. (2018). An introduction to immunology and immunopathology.
Allergy Asthma Clin. Immunol.
14 (Suppl. 2): 49.
Matejuk, A. (2018). Skin immunity.
Arch. Immunol. Ther. Exp. (Warsz.)
66: 45.
Pasparakis, M., Haase, I., and Nestle, F.O. (2014). Mechanisms regulating skin immunity and inflammation.
Nat. Rev. Immunol.
14: 289.
Richmond, J.M. and Harris, J.E. (2014). Immunology and skin in health and disease.
Cold Spring Harb. Perspect. Med.
4: a015339.
Simoes Quaresma, J.A. (2019). Organization of the skin immune system and compartmentalized immune responses in infectious diseases.
Clin. Microbiol. Rev.
32: e00034.
Smith, A.R., Knaysi, G., Wilson, J.M., and Wisniewski, J.A. (2017). The skin as a route of allergen exposure: part I. Immune components and mechanisms.
Curr. Allergy Asthma Rep.
17: 6.
2 How to Get the Most Out of Your Dermatologic History and Examination
Michelle Woodward O’Gorman
KEY POINTS
Listen carefully and attentively to the owner.
It is difficult to diagnose many dermatologic diseases without a good history.
Since dermatologic histories can be long, clients should fill out a dermatology history form before their appointment.
Examine patients’ skin in a systematic way so no area is overlooked.
Be sure to record findings in a detailed manner.
Like many areas of veterinary medicine, dermatology relies on the history and physical exam to form a clinical picture. If time is dedicated to these early in a case, the clinician will have an easier time selecting and interpreting diagnostics later. A practiced dermatologist will frequently have a good clinical picture formed based on history alone, even before evaluating the patient. This can prompt the clinician to ask specific questions and more carefully evaluate certain areas of the body, although care must be taken to avoid tunnel vision.
