Hypersensitivity Skin Disorders

By | March 6, 2016

Clinical hypersensitivity disorders have been classified by Gel and Coombes. The following description is simplified since in many instances complex interactions occur simultaneously.

Type 1 (immediate, anaphylactic)

  • genetically susceptible individuals inhale (absorb percutaneously?) allergens such as pollen and house dust, and produce immunoglobulin E (IgE), which fixes to tissue mast cells and blood basophils
  • the allergen subsequently comes into contact with its specific IgE, leading to the release of vasoactive amines, which cause tissue damage
  • examples are urticaria, angio-oedema, atopy, drug eruption and flea-bite hypersensitivity

Type 2 (cytotoxic)

  • IgG or IgM with or without complement binds to complete antigens on body tissues
  • the antigen—antibody reaction causes cell lysis
  • examples are pemphigus, pemphigoid, cold agglutinin disease and dnig eruption

Type 3 (immune complex)

  • circulating antigen-antibody complexes fix complement and are deposited in blood vessel walls
  • these complexes attract neutrophils; proteolytic and hydrolytic enzymes released from the neutrophils produce tissue damage
  • examples are systemic lupus erythematosus and bacterial hypersensitivity

Type 4 (delayed)

  • incomplete allergen (hapten) combines with tissue protein, e.g. collagen; this complete allergen is processed by monocytes, macrophages or Langerhans cells and sensitizes T-lymphocytes
  • sensitized T-lymphocytes respond to subsequent challenge by releasing lymphokines, which produce tissue damage
  • an example is contact hypersensitivity

Urticaria (hives)

  • seen in dogs and cats
  • uncommon
  • type 1 and 3
  • many possible causes — e.g. drugs, vaccines, insect bites or stings, infections

Clinical features

  • acute onset
  • localized or generalized wheals
  • hair in affected lesions stands up
  • variable pruritus

Diagnosis

  • history
  • physical examination
  • investigation of possible underlying causes

Differential diagnosis

  • superficial folliculitis
  • cutaneous neoplasia
  • dermatophyte infection
  • demodicosis

Treatment

  • establish the underlying cause if possible and remove it
  • glucocorticoids given systemically — drug of choice is pred-nisolone at a dose of 2 mg/kg for a few days

Angio-oedema (angioneurotic oedema)

  • dogs and cats
  • type 1 hypersensitivity
  • commonly due to wasp and bee stings, but other causes as for urticaria
  • cutaneous response is more dramatic than with urticaria, with extreme swelling of the face, head or feet
  • laryngeal oedema may occur

Diagnosis

  • history (e.g. seen playing with a wasp)
  • physical examination

Treatment

  • elimination of known cause
  • adrenaline 1:1000, 0.1-0.5 nil subcutaneously
  • glucocorticoid therapy as for urticaria — intravenous route preferred
  • consider tracheotomy if severe laryngeal oedema

Atopy (atopic disease)

  • denned as an inherited predisposition to develop IgE antibodies to environmental allergens resulting in allergic disease ()
  • common
  • occurs in dogs and cats
  • many allergens may be responsible, including:
  • house dust
  • house dust mite
  • human dander
  • animal dander
  • pollens
  • fungi
  • moulds
  • feathers

Canine atopy

Clinical features

  • most cases begin symptoms between 1 and 3 years of age with a range of 6 months to 7 years
  • clinical signs may be seasonal at first but many dogs develop hypersensitivity to further allergens and symptoms then persist all year round. Other dogs have a history of non-seasonal symptoms from the start
  • pruritus is the principal complaint
  • typically the sites affected are the face, the ventrum and axilla, and the feet ()
  • there may be erythema, but most lesions seen are secondary; these consist of pyoderma, seborrhoea, lichenification (in more chronic cases) and alopecia. Self-trauma is common and may confuse the clinical picture
  • other features which may be seen include salivary staining of the coat as a result of constant licking, conjunctivitis, otitis externa and hyperhidrosis (sweating)

Diagnostic procedures

  • in order to minimize poor results it is important to select cases carefully prior to performing intradermal testing; an intelligent, operative owner aware of the complexities of investigation is also useful

Pre-testing investigations

  • history and physical examination should suggest atopy; do not test every pruritic dog without a careful history and physical examination
  • rule out parasitic involvement, particularly scabies and fleas. Although atopic dogs are predisposed to develop flea-bite hypersensitivity, if fleas are present these should be eliminated prior to performing intradermal testing so that the relative importance of the fleas in inducing pruritus can be ascertained. If there is any doubt at all concerning scabies, a therapeutic trial is useful before proceeding any further. Such procedures also allow time for any glucocorticoids which may have been previously administered to be eliminated from the system
  • seborrhoea and pyoderma are treated to ensure that they are not the primary cause of the pruritus. If pruritus ceases with proper treatment of pyoderma and seborrhoea, it is unlikely that atopy is an underlying cause and another line of investigation will be needed
  • dietary investigations are routinely performed prior to skin testing to rule out food hypersensitivity ()
  • ensure that no anti-inflammatory dnigs have been administered recently. It is difficult to make precise recommendations as to how long to wait prior to testing. This will depend on the length of time glucocorticoids have been given. If repositol glucocorticoids have been used, there may be a wait of some months before positive reactions will occur. For this reason and for others discussed elsewhere in this book, repositol glucocorticoids are to be avoided in the management of pruritic skin conditions in the dog

Allergen selection

  • consult with physicians to determine what allergens are common in the locality
  • use standardized veterinary aqueous allergens only; these are currently not available in the United Kingdom. Reliable allergens are available from HAL Laboratories (Haarlem, Holland) or Greer Laboratories (Lenior, N.C., USA)

Technique of intradermal allergy testing

  • the dog is placed in lateral recumbency and the hair of the flank is carefully clipped. Xylazine hydrochloride (Rompun, Bayer, UK) 0.45 mg/kg intravenously with 0.04 mg/kg atropine sulphate sub-cutaneously is used for sedation except in calm individuals. Other sedatives are not indicated as they will interfere with reactions
  • a felt-tipped pen is used to mark each injection site
  • 0.05 ml of each test allergen is injected intradermally, using a 26-gauge needle. A positive control injection (0.05 ml of 1:100000 histamine phosphate) and negative control (0.05 ml of diluent) is also injected
  • the injection sites are examined 15 and 30 minutes later
  • a positive reaction is a wheal equal to or larger in diameter than
  • the difference between the positive and negative controls ()
  • positive reactions should be compared with the allergens known to be in the dog’s environment as established in the history
  • there are many pitfalls associated with allergy testing and both false positive and false negative reactions may occur
  • the commonest causes of false positive reactions are irritant allergens containing glycerine, trauma with too large a needle, injection of irritant contaminants, injection of too large a volume, and injecting into already inflamed skin
  • some causes of false negative reactions include subcutaneous injection, using too-weak allergens (out of date, mixes), and interference from previously administered glucocorticoids or antihistamines

Radioallergosorbent Test

  • the radioallergosorbent test (RAST) is an in vitro test which has recently become available commercially in the USA
  • RAST measures the concentration of canine allergen-specific IgE in serum
  • correlation with intradermal testing is variable, in some instances being good and in others poor. In addition high levels of background IgE may limit the usefulness of the test. Refinement of the test in the future may greatly increase its value, although at the time of writing most authorities prefer intradermal allergy testing
  • Willemse () has suggested major and minor features in order to clarify the diagnosis of atopy.

Major Features

At least three should be present:

  • a breed predilection
  • a familial history of atopy
  • pruritus
  • facial and/or digital involvement
  • chronic or chronically relapsing dermatitis
  • lichenification of the flexor surface of the tarsus or the extensor surface of the carpus

Minor Features

At least three should be present:

  • onset before 3 years of age
  • conjunctivitis
  • facial erythema and cheilitis
  • superficial pyoderma
  • hyperhidrosis
  • positive intradermal allergy testing
  • elevated allergen-specific IgE
  • elevated allergen-specific IgGd

Differential diagnosis

  • flea-bite hypersensitivity
  • food hypersensitivity
  • contact hypersensitivity
  • scabies
  • other diseases leading to secondary pyoderma
  • hookworm dermatitis
  • subcorneal pustular dermatitis

Treatment

  • avoidance of allergens is occasionally beneficial if only one or two allergens are involved, for example exclude from the bedroom in dust hypersensitivity
  • systemic glucocorticoids: prednisolone is the drug of choice. It must be given on alternate days, thus minimizing the risk of adrenal cortex suppression. Therapy is lifelong
  • antihislamines: these drugs are not particularly effective but their trial use is warranted, since some cases benefit. Various antihislamines should be tried, as some cases will respond to one type while others respond to a different drug
  • hyposensitizalion: repeated injections of initially increasing amounts of allergen are given in an attempt to modify the immune response. The mode of action is unclear, but placebo-controlled double-blind trials have demonstrated their effectiveness (). A satisfactory response may take up to 9 months, and definitive conclusions as to effectiveness in any one particular case should not be made before this time. It is therefore important to pick cases and owners carefully and explain procedures in detail before attempting hyposensitization in order to maximize the possibility of success
  • low-dose alternate-day prednisolone may be used in conjunction with hyposensitization in severe cases
  • approximately 50% of atopic dogs benefit to some extent from hyposensitization in that either glucocorticoid therapy is no longer needed or a reduced dose will control symptoms
  • essential fatty acid supplementation (EFAs)
  • EFAs have recently become available in the UK (Efavet, Efamol) for the treatment of atopy. These substances have been shown to modify inflammation by promoting anti-inflammatory prosta-glandins and inhibiting the production of pro-inflammatory substances such as thromboxanes and leucotrienes. Some cases, but not all, are controlled well by the use of essential fatty acids, which thus offer a safe alternative to glucocorticoids

Feline atopy

  • increasingly recognized world-wide including the UK

Clinical features

  • seasonal or non-seasonal
  • facial pruritus
  • pruritic ears
  • miliary dermatitis-like lesions
  • indolent (‘rodent’) ulcer, eosinophilic plaque or granuloma
  • symmetric alopecia
  • generalized pruritus

Diagnosis

  • history
  • physical examination
  • investigation of other causes of the clinical features listed
  • intradermal allergy testing. Reactions tend to be more diffuse than in dogs and hence more difficult to interpret

Treatment

  • prednisolone 2 mg/kg initially, then when control is achieved given on an alternate-day basis
  • essential fatty acid supplementation (Efavet, Efamol). Preliminary work suggests that this approach is promising, although controlled trials have not yet been performed in cats

Food hypersensitivity (food allergy)

  • uncommon
  • dogs and cats
  • thought to involve type 1, 2 and 4 hypersensitivity reactions
  • hypersensitivity usually develops to specific items in the diet, such as beef, fish, milk. Change of diet prior to the onset of symptoms is not significant since the allergen has frequently been a component of the animal’s diet for months or years before the commencement of symptoms

Clinical features

  • any age, sex, breed
  • symptoms are variable, and the condition can mimic any dermatosis

Dogs

  • pruritus
  • pruritic superficial folliculitis
  • seborrhoea
  • urticaria

Cats

  • miliary dermatitis-like lesions
  • facial dermatitis ()
  • generalized pruritus
  • seborrhoea
  • urticaria
  • psychogenic alopecia
  • indolent ulcer
  • eosinophilic plaque/granuloma

Diagnosis

  • history
  • physical examination
  • dietary investigation
  • a detailed list is made of the animal’s diet
  • protein sources unfamiliar to the animal, such as cooked lamb or chicken plus rice, are fed to the exclusion of all other food for two weeks. Emphasize to the owner that all members of the family, including children, must understand that no other scraps of food must be given at this time
  • improvement while on the hypoallergenic diet suggests food hypersensitivity. Individual items are then added to the diet every week; relapse followed by remission when the food item is removed again identifies the allergen
  • note that changing from one brand of commercial food to another is not helpful since the offending allergen is likely to be in both brands
  • intradermal allergy testing is of no value in the diagnosis of food hypersensitivity

Differential diagnosis

Dogs

  • atopy
  • flea-bite hypersensitivity
  • scabies
  • superficial folliculitis
  • pediculosis
  • intestinal parasitic hypersensitivity
  • seborrhoea
  • drug hypersensitivity

Cats

  • atopy
  • flea-bite hypersensitivity
  • cheyletiellosis
  • pediculosis
  • dermatophyte infection
  • drug hypersensitivity
  • intestinal parasitic hypersensitivity
  • trombiculidiasis
  • psychogenic alopecia

Treatment

  • avoid the specific allergen in the diet
  • if this is not identified, feed the hypoallergenic diet used to investigate the cause. This diet will need to be balanced with mineral and fatty acid supplements
  • in both dogs and cats there is frequently a poor response to glucocorticoids

Contact hypersensitivity (allergic contact dermatitis)

uncommon (primary irritant dermatitis more common)

dogs and cats

type 4 hypersensitivity

many substances have been incriminated in contact hypersensitivity. Examples of allergens are:

  • pollens and resins
  • soaps
  • shampoos
  • topical ointments, especially those containing neomycin
  • insecticides
  • disinfectants
  • flea collars
  • wool, nylon fibre
  • dyes, mordants, finishes used in the manufacture of carpets and
  • blankets rubber and plastic

Clinical features

  • hypersensitivity usually develops to a substance which the dog or cat has been in contact with for at least 6 months. Hence a history of recent change of bedding or carpets is not generally significant
  • lesions occur in contact sites (): the ventral abdomen, feet, scrotum, chin, neck and pinnae. If a plastic dish is involved lesions occur around the mouth and nose
  • lesions may be seasonal or non-seasonal and consist of erythema, macules and papules in acute cases, and hyperpigmentation in chronic cases. Self-trauma and secondary pyoderma are common
  • pruritus varies from mild to extreme

Diagnosis

  • history
  • physical examination
  • elimination and provocative exposure:
  • the animal is kept away from suspect allergens for 2 weeks, for example kept off grass, or housed in the kitchen and not allowed in the rest of the house
  • if there is contact hypersensitivity there is remission of clinical signs followed by relapse when the animal comes back into contact with the allergen. Individual items, such as carpets, bedding, are exposed to the animal item by item for a week at a time. (Remember that contact hypersensitivity is a delayed response, and that reactions will not occur in less than 48 hours)
  • an intelligent co-operative owner is required for the above investigation or failure to identify the allergen will be inevitable

Patch Testing

  • Patch testing is theoretically the best method to diagnose contact hypersensitivity and is the standard approach in man. In animals it is difficult to get the animal’s co-operation. Two nethods have been advocated

Closed patch testing

  • suspect allergens are placed in close contact with skin on the flank after clipping
  • in order to facilitate close contact between the allergens and the skin, Finn chambers may be used. These are obtained from Associated Hospital Supplies (PO Box 4, Pershore, Worcestershire, UK). Finn chambers are shallow metal containers mounted on Scampor (non-woven microporous adhesive tape). The suspect allergen is placed in each chamber, and the supporting tape fixed to the flank by means of a body bandage
  • Elizabethan collars may be needed to prevent interference by the animal
  • the chambers are removed after 48 hours and the animal examined for positive reactions, which tend to be mild erythema. Doubtful cases are examined again at 72 hours

Open patch testing

the test material is applied to the clipped skin and the solvent allowed to evaporate

suggested allergen concentrations have been given by Walton

the test site is examined after 48 hours, positive reactions showing as erythema

Differential diagnosis

  • primary irritant contact dermatitis
  • atopy
  • food hypersensitivity
  • scabies
  • Pelodera dermatitis
  • hookworm dermatitis
  • superficial pyoderma

Treatment

  • avoid the offending allergen
  • glucocorticoids — response is variable and rarely totally satisfactory
  • hyposensitization is not effective

Drug eruption

  • rare
  • cutaneous or mucocutaneous reaction to a drug
  • dogs and cats
  • thought to be associated with all types of hypersensitivity reactions
  • the reaction may occur even though the drug has been administered long-term to the animal without previous problems, or it may occur after only a few days of administration

Clinical features

  • lesions are very variable and may mimic virtually any dermatosis
  • possible lesions include: papules, seborrhoea, vesicles, alopecia, ulceration, urticaria and otitis externa

Diagnosis

  • history
  • physical examination
  • biopsy: perivascular dermatitis, subepidermal vesicular dermatitis, intraepidermal vesiculopustular dermatitis
  • response to removal of the drug
  • do not readminister the drug to determine whether a relapse occurs; this may provoke anaphylaxis

Differential diagnosis

  • virtually any dermatosis

Treatment

  • discontinue the offending drug and avoid drugs of the same group
  • symptomatic therapy, bathing and antibacterial agents
  • glucocorticoids are frequently not effective

Intestinal parasitic hypersensitivity

  • uncommon
  • dogs and cats
  • immunology poorly understood; possibly involves type i hypersensitivity

Clinical features

  • lesions are usually pruritic crusting papules or seborrhoea
  • elimination of parasites is followed by recovery; relapse if reinfestation occurs

Diagnosis

  • history
  • physical examination
  • faecal examination
  • response to treatment

Treatment

  • elimination of parasites

Hormonal hypersensitivity

  • rare
  • dogs
  • immunology poorly understood; possibly type i and 4 reactions to progesterone, oestrogen or testosterone

Clinical features

  • no breed or age predilection, but most cases reported in intact females
  • pruritic, papulocrustous lesions of perineal, genital and thigh regions
  • the lesions are bilaterally symmetrical and may spread to involve the feet, face and ears in advanced cases
  • there may be enlargement of the nipples and vulva
  • there are often irregular oestrus cycles or pseudopregnancy

Diagnosis

  • history
  • physical examination
  • intradermal testing with aqueous progesterone (0.025 mg), oestrogen (0.0125 mg), or testosterone (0.05 mg). Check for immediate and delayed hypersensitivity reactions
  • response to therapy

Differential diagnosis

  • flea-bite hypersensitivity
  • food hypersensitivity
  • atopy
  • folliculitis
  • drug eruption
  • ovarian imbalance type 1
  • intestinal parasitic hypersensitivity

Treatment

  • neuter
  • female dogs may respond to testosterone, but this is only of use to reduce pruritus prior to ovariohysterectomy

Flea-bite hypersensitivity

  • This is discussed under parasitic conditions ().

 

Selections from the book: “Skin Diseases in the Dog and Cat”. D. I. Grant, BVetMed (1991)