Skin: atopy

Contributors: David Godfrey, Rosanna Marsella, Richard Squires

Species: Canine | Classification: Diseases

Introduction Pathogenesis Diagnosis Treatment Outcomes Further Reading

Introduction

Cause: inherited predisposition to develop hypersensitivity-mediated skin disease against environmental allergens.
Signs: pruritic skin disease (may be seasonal), recurrent skin and ear infections.
Diagnosis: suggestive history, compatible clinical signs and exclusion of other pruritic skin diseases.
Treatment: desensitization or symptomatic management.
Prognosis: guarded - problems likely to persist lifelong.
Print off the owner factsheet on Atopy Atopy to give to your client.

Presenting Signs

Pruritus affecting the face, feet, pinnae, ventral abdomen and axillae; usually sparing the dorsum.

Advanced cases show lesions of self-trauma (saliva staining on hairs, excoriation, hair loss, hyperpigmentation, and lichenification).
Chronically relapsing skin infections.

Otitis externa Skin: otitis externa.
Bilateral conjunctivitis Conjunctivitis.

Geographic Incidence

Atopy is universally recognized, probably affecting 10% of canine population.

Age Predisposition

Signs are expected to start between 6 months and 2 years of age and often worsen as the dog matures.
Significant numbers of affected dogs only have serious signs when older but have had milder signs when young.
They will usually persist for life.

Breed Predisposition

Breed predispositions seems to vary according to populations and geography. The following breeds have been suggested to be predisposed by studies that have included a control group.

Cairn Terrier Cairn Terrier.
West Highland White Terrier West Highland White Terrier.
Shar Pei Chinese Shar Pei.
Scottish Terrier Scottish Terrier.
Lhasa Apso Lhasa Apso.
Wire-haired Fox Terrier Fox Terrier - Wire.
Dalmatian Dalmatian.
Boston Terrier Boston Terrier.
Boxer Boxer.
Labrador Retriever Retriever: Labrador.
Bulldog Bulldog.
English Setter English Setter.

Miniature Schnauzer Schnauzer: miniature.
Shih Tzu Shih Tzu.
Pug Pug.
Irish Setter Irish Setter.
Cocker spaniel English Cocker Spaniel.
Beauceron Beauceron.
Yorkshire terrier Yorkshire Terrier.

Cost Considerations

Very variable according to severity and seasonality of the signs and the ability of the owner to perform some cheaper treatments such as washing.
The diagnostic protocol can be lengthy and expensive.
Needs life-long management regimes which may be costly.

In dogs with seasonal pruritus, inexpensive treatment will often control the problem.

Pathogenesis

Etiology

Unknown: thought in part to be associated with dysregulation of cytokine production and alterations in T-cell subset populations.
Abnormal epidermal integrity is also probably important.

Predisposing Factors

General

Familial history of atopy.

Some studies show a link between month of birth and development of atopy. Dogs born during the pollen season may become sensitized in the first few months of life.
Parasites may increase the dog's production of IgE to other environmental allergens.
Viral infection or vaccination also increase production of IgE to environmental allergen.
Being raised in a rural environment may protect against the development of atopic dermatitis.

Pathophysiology

Still poorly understood. There seems to be both epithelial barrier function and immunological abnormalities.
There is an imbalance in T-cell populations and aberrant cytokine production.
Antigen-presenting cells stimulate the production of T helper 2 cells both locally and at distant lymph nodes → stimulate IgE-producing B cells, producing interleukins → mast cell and eosinophil.
Mast cell degranulation releases vasoactive factors → start of the inflammatory cascade.
The corneocytes of atopic dogs have greater adherence for Staphylococcus pseudintermedius Staphylococcus intermedius , → the high frequency of development of secondary pyoderma Skin: bacterial skin disease - overview.

A defective epidermal barrier allows percutaneous absorption of allergen. The allergen contacts allergen specific IgE on Langerhans' cells. Allergens are trapped, processed, and presented to allergen specific T lymphocytes. This results in increased numbers of T helper 2 cells which produce interleukins. Ultimately, there is enhanced production of allergen specific IgE by B lymphocytes.

Aeroallergens

Indoor allergens appear important throughout the world:
- House dust mites - Dermatophagoides farina, D. pteronysinus and possibly Blomia tropicalis and Euroglyphyus maynei.
- Storage mites - Acarus siro, Tyrophagus putrescentiae and Lepidoglyphus destructor are of less certain signifcance.
Pollens are important in Australia and North America and may be less commonly important in Europe.
Molds are uncommonly important allergens.
Malassezia is sometimes used in immunotherapy.
Danders from other mammals, and bird feather allergens are sometimes included.

Timecourse

Disease is uncommon <6 months of age (except in Shar Pei - seen earlier).
Signs worsen with age.
Disease that starts seasonally often becomes year round.
Secondary pyoderma or Malassezia Skin: malassezia disease disease is often a significant part of disease.

Diagnosis

Presenting Problems

Pruritus - particularly when affecting the feet, inside of the legs, ventrum, face, the ventral side of the pinnae and the ear canals.
Rule outs:
- Parasitic disease:Sarcoptes scabiei Skin: sarcoptic mange ,Cheyletiellaspp Skin: cheyletiellosis , Demodicosis Skin: demodectic mange , Trombicula autumnalis Skin: neotrombicula autumnalis infestation , lice Skin: pediculosis , fleas Skin: flea bite hypersensitivity.
- Infection: bacterial pyoderma Skin: bacterial skin disease - overview , Malassezia spp Skin: malassezia disease (although these are often seen secondary to allergic skin disease), dermatophytosis Skin: dermatophytosis - particularly Trichophyton spp Trichophyton spp.
- Other allergic disease: food sensitivity Skin: food hypersensitivity , flea allergic dermatitis Skin: flea bite hypersensitivity , contact hypersensitivity or irritant Skin: allergic contact dermatitis.
- Other: drug eruption Skin: toxic epidermal necrolysis.

Client History

Pruritus is expected in skin allergies.

Foot licking.
Face rubbing.
Licking and scratching at abdomen.
Head-shaking and ear scratching.
Recurrent dermatitis since a young age. Onset up to 3 years.
Seasonal recurrence - may be associated with increased indoor activity (in the case of house dust mite allergy) or outdoor activity (where there is allergy to pollens).
Some pollen-allergic patients show non-seasonal signs because of multiple allergies to plants with different pollination periods.

Recurrent otitis.
Hair loss, especially ventrally.
Familial history of atopy +/- a breed predisposition.
Irregular estrous cycles, low conception rates and false pregnancy Pseudopregnancy (false pregnancy or pseudocyesis). have not been proven to be associated with atopy.

Clinical Signs

Diagnosis is clinical and by exclusion of other pruritic skin diseases.
Facial erythema and pruritus .
Pedal erythema and pruritus .
Ventral erythema .
Secondary staphylococcal pyoderma .
Pinnal erythema.
Lichenification of the flexor surface of the tarsal joint and/or the extensor surface of the carpal joint .
Chronic or chronically relapsing dermatitis.

Salivary staining of coat.
Otitis externa .
Hyperhidrosis.
Conjunctivitis.
Lichenification .
Alopecia.

Rhinitis.
Asthma.
The severity of clinical signs may be recorded using a scoring system. Various systems of different complexity have been described, the latest being CADESI-4.
It is important to distinguish between acute and chronic atopic dermatitis as they have different interventions Skin: atopy - anti-inflammatory therapy:
- Acute disease is shown by puritus, erythema and excoriation.
- Chronic disease also has lichenification and often secondary bacterial and/or Malassezia dermatitis.

Diagnostic Investigation

Microscopy/cytology

To help rule out parasitic differentials.
To help rule out primary microbial infections - bacteria or yeasts and to identify secondary complications of atopic dermatitis.

Bacteriology

Culture Bacteriology:
- Skin swabs for culture to identify and allow control of bacterial infection if identified by cytology and if antibiotic treatment is being contemplated.
- Culture without prior or concurrent cytology is very difficult to interpret as positive cultures will be found sampling normal skin.

Other

For hyposensitization with allergen-specific immunotherapy (ASIT) Allergen-specific immunotherapy identification of offending allergen is necessary:
- Intradermal testing Skin: intradermal test.
- In vitro test for allergen-specific serum IgE levels.

Allergy testing Allergy testing is not used to diagnose or rule out atopic dermatitis, rather it is used once a diagnosis has been established and to aid treatment - allergen avoidance or ASIT.

Corticosteroid administration should usually be withdrawn BEFORE allergy testing as this gives greater confidence that a negative test is a true negative - advice should be sought from the dermatologist or laboratory running the test but withdrawal periods range from 14-90 days depending on product used.
Other than progestagens no other agents affect serological allergy testing:
- Ciclosporin does not need withdrawal.
- Oclacitnib use for 2 weeks does not require withdrawal but longer treatment periods have not been evaluated for their effects on allergy testing. Antihistamines must be withdrawn for 2 weeks prior to intradermal testing.
- Lokivetmab Lokivetmab does not need to be withdrawn.

Histopathology Findings

Histopathology is not useful in positively diagnosing atopic dermatitis and skin biopsy is not part of an "allergy work up".
It may be useful in ruling out other differentials.
It may be useful to diagnose pyoderma or Malassezia infection but this usually is better done in other ways, eg cytology.
Superficial perivascular dermatitis, lymphocytes and histiocytes predominate in skin allergy but are non-specific.

Differential Diagnosis

Pruritus

Flea allergy Skin: flea bite hypersensitivity.
Sarcoptic mange Skin: sarcoptic mange.
Demodectic mange Skin: demodectic mange.
Dermophytosis (especially Trichophyton spp Trichophyton spp Skin: dermatophytosis.
Bacterial folliculitis Skin: bacterial folliculitis.

Adverse reaction to food Skin: food hypersensitivity.
Cheyletiellosis Skin: cheyletiellosis.

Malassezia dermatitis Skin: malassezia disease.
Pediculosis Skin: pediculosis.
Drug eruption Skin: toxic epidermal necrolysis.

Contact hypersensitivity Skin: allergic contact dermatitis.
Intestinal parasite hypersensitivity.

Treatment

Standard Treatment

Using evidence-based veterinary medicine, studies have shown benefits of systemic steroids and ciclosporin, topical tacrolimus Tacrolimus , oclacitinib Oclacitinib and lokivetmab.
See Skin: atopy - anti-inflammatory therapy Skin: atopy - anti-inflammatory therapy Anti-inflammatory treatment options.
There is weaker evidence supporting the use of ASIT, topical trimancinolone Triamcinolone spray, oral pentoxifylline Pentoxifylline, gamma interferon Interferon and oral misoprostol Misoprostol. These last 3 treatments are not routinely used currently.
The International Task Force on Veterinary Dermatology (now International Committee on Allergic Diseases of Animals, ICADA) has recommended that most dogs should have immunotherapy unless their signs are mild or restricted to a short season. This is because it is the only treatment that can resolve the problem rather than hide the clinical signs.
Control secondary bacterial infections - usually using topical antiseptics but systemic antibiotics chosen after cytology and culture and sensitivity are sometimes needed.
Control of secondary Malassezia infection may be necessary long-term in some dogs, both topical and systemic medications are useful.
Address concurrent allergies, ie adverse reaction to food or flea bite hypersensitivity.

Allergen avoidance has a small part to play in management of atopic dogs Skin: atopy - allergen avoidance.
Antihistamines Therapeutics: skin are probably variably effective. There are actually no scientific studies that support their use but they are favored for long-term control by some experienced owners of atopic dogs. Several may need to be tried in an individual. They are more effective in preventing pruritus than in initially bringing it under control and might be more helpful as a treatment to reduce the required dose of, eg systemic steroids.
Topical therapy is valuable in reducing the allergenic load on the skin, normalizing the skin barrier, soothing and reducing seconday infection.
Leave-on conditioners with glucocorticoids are effective and do not suppress adrenal glands (not available in the UK).
Essential fatty acid supplementation Omega-3 fatty acids , enriched foods or application on to the skin have weak evidence to support their use. They have a low risk of side effects but can have a significant cost and might be more helpful as a treatment to reduce the required dose of, eg systemic steroids.

Monitoring

Monitoring response to treatment can be achieved both by the owner judging the level of pruritus at home and by the clinician judging the severity of skin lesions. The CADESI-4 score can be used by the clinician but it is very useful for clients to keep a pruritus diary and to record the level of pruritus each day, eg using a score out of 10 with 0-1 being normal and 10/10 being a constant itch. A similar score can be made using a Visual Analog Score (VAS) system - the owner places a mark on a 10 cm long line indicating the degree of itch.
Side-effects of glucocorticoid medication Prednisolone. Long-term use should prompt routine urinanalysis.
Avoidance of flare factors is vital, eg staphylococcal pyoderma, Malassezia or fleas.

Subsequent Management

Treatment

See Skin: atopy - anti-inflammatory therapy Skin: atopy - anti-inflammatory therapy for details of using corticosteroids, oclacitinib, ciclosporin and tacrolimus.
Long-term use of antibacterial shampoos may result in secondary seborrhea necessitating changes of product or adding in a conditioner.
Increase in itch should prompt search for flare factors - parasite infestation, bacterial infection or yeast infection.
Hyposensitization regimes may take up to 9 months to take effect.

Monitoring

Pruritus decreased.
Normalization of skin and haircoat.
Change in behavior so that the dog is more settled and "happier".

Outcomes

Prognosis

Good if seasonally affected; 90% can be satisfactorily controlled.
Many develop multiple allergies over succeeding years → increased difficulty in control.
Cost and time implications for owners of severely affected dogs may lead to requests for euthanasia.

Expected Response to Treatment

Reasons for Treatment Failure

Failure to diagnose concurrent disease, especially flea allergy, food sensitivity, pyoderma, Malassezia dermatitis.
Many cases become less responsive to glucocorticoids with the passage of time - frequently due to a failure to manage concurrent disease.
Inability of client to cope with treatment schedules.
Expense of those treatments with minimal side effects may lead to some owners having to use less effective and more dangerous interventions.

Introduction

Presenting Signs

Geographic Incidence

Age Predisposition

Breed Predisposition

Cost Considerations

Pathogenesis

Etiology

Predisposing Factors

Pathophysiology

Aeroallergens

Timecourse

Diagnosis

Presenting Problems

Client History

Clinical Signs

Diagnostic Investigation

Microscopy/cytology

Bacteriology

Other

Histopathology Findings

Differential Diagnosis

Treatment

Standard Treatment

Monitoring

Subsequent Management

Treatment

Monitoring

Outcomes

Prognosis

Expected Response to Treatment

Reasons for Treatment Failure

Further Reading

Publications

Refereed papers

Other sources of information

Other Sources of Information