Hypersensitivity of dog skin to fleas-a clinical report

J . small Anim. Pract. (1975) 16, 317-327.

Hypersensitivity of dog skin to fleas-a clinical report

K . P. B A K E R * A N D J . O ’ F L A N A G A N ? .

* Faculty of Veterinary Medicine, University of Dublin, Ballsbridge, Dublin, 4 and t Department of Veterinary Medicine, Pharmacology and Food Hygiene,

Faculty of Veterinary Medicine, Ballsbridge, University College, Dublin, 4. (Present address: 8, Portreath Drive, Darley Abbey, Derby)

A B S T R A C T

The results of an examination of the clinical signs, epidemiology and histopathology of dogs presented with flea bite dermatitis at two Dublin clinics are given. Whilst the majority of Dublin dogs are infested with fleas only some develop a reaction to flea saliva.

I t is concluded that on the evidence available, flea dermatitis is a hypersensitive reaction to flea saliva and elimination of fleas from the environment of affected animals remains the best method of controlling the disease.

I N T R O D U C T I O N

Fleas are the commonest ectoparasites of dogs in Ireland and the reaction to their saliva is the most important cause of skin disease in dogs attending the small animal clinic at the School of Veterinary Medicine in Dublin (Baker & Hatch, 1972). The condition has a number of synonyms, viz. summer eczema, pyotrau- matic dermatitis, flea allergy dermatitis, and flea hypersensitivity. It is characterized by intense pruritus in the areas most favoured as feeding sites by fleas; the primary lesion is erythema with a papular reaction. Self-excoriation, resulting from the pruritus, produces hair breaking and local alopecia. Occasionally severe reactions result in an area of serous dermatitis 3-10 cm in diameter (acute wet eczema). Animals affected for a number of years develop alopecia and chronic thickening of the skin of the dorsum of the trunk. The disease is progressive and is most noticeable in the warmer months.

Earlier published reports support the contention that the clinical signs result from a hypersensitivity reaction to flea saliva (Muller, 196 1 ; Kissileff, 1962 ;

317

318 K . P . B A K E R A N D J . O ’ F L A N A G A N

Sertid, 1965; Schwartzman & Orkin, 1962; Muller and Kirk, 1969). The reaction of the guinea-pig to flea bites has been extensively studied (Benjamini et al., 1960, 1961, 1963). However, many practitioners still attribute the disease to food allergy, intestinal parasites and other causes. In the authors’ opinion the available evidence indicates that the disease is an allergic reaction in the skin to flea saliva. The following report is based on a study of cases in dogs of hypersensitivity to fleas submitted for examination to two clinics in Dublin. Clinical data and results of skin biopsy are reported.

M A T E R I A L S A N D M E T H O D S

The disease has been studied in the clinic of the University of Dublin and at a free clinic of an Animal Welfare Society in Dublin. Dogs examined comprised pedi- gree, crossbreds and mongrels. Intra-dermal tests with whole flea extract were undertaken in sixty-eight affected animals using a technique described elsewhere (Baker, 1971). On two occasions skin was taken from the sites of positive reactions to an intra-dermal injection of whole flea extract and stained with haematoxylin and eosin. Skin biopsies were also taken from early cases, those with an acute serous dermatitis, and from chronic cases. Sections were stained with haematoxylin and eosin, toluidine blue and carbol chromatrope.

To determine the age at which clinical signs of the disease were first observed records of the first one hundred cases were examined. Results are given in Table 1.

Epidemiology Most dogs submitted to the two clinics in the warmer months of the year showed

evidence of flea infestation to a variable extent. However, only a small proportion of the population develop a reaction to flea saliva. Some individuals, therefore, show idiosyncracy to flea saliva. Repeated challenge is presumably required for this to develop for clinical signs have not been observed in dogs younger than 5 months of age. Most cases develop in the first 5 years of life (Table 1).

TABLE 1. Age a t which clinical signs were first observed

1 year 1-6 years 6-10 years 10 years

No. of dogs 6 57 34 3

A comparable age incidence has been reported in the United States of America (Muller, 1961).

No lesions have been observed in the first 5 months of life, so apparently a latent period must elapse before clinical signs appear. I n the production of experimental lesions of the skin of guinea-pigs repeated exposure to flea saliva is required before signs appear (Larivee et al., 1964), the so-called induction or first phase.

H Y P E R S E N S I T I V I T Y O F D O G S K I N T O F L E A S 319

No sex incidence was observed in the sample population of one hundred. Muller & Kirk (1969) record no breed or sex predilection. But Muller (1961) reports that fleas prefer long-haired dogs as hosts. In his study 78% of all cases of flea allergy dermatitis were long haired. However, a reverse picture is seen in Dublin with sixty-seven of one hundred cases occurring in short-haired dogs. This probably has no significance for the ratio of long-haired to short-haired dogs attending the two clinics in Dublin is 1 : 2. Muller does not give the population ratio of long-haired to short-haired dogs in his clinic.

Whilst fleas may be found on dogs throughout the year in Ireland they are far less common during the winter months. Some correlation with this is seen when the seasonal incidence of the disease is examined (Table 2 ) .

TABLE 2. Onset of clinical signs in 100 cases randomly selected

Number Ave. temp. presented Dublin*

Dec.-Feb. 9 5.2"C. Mar.-May 24 8.6%. June-Aug. 28 I5.0"C. Sept .-Nov. 39 10.4%.

* Department of Transport and Power- Meteorological Service, Dublin

Though cases occur throughout the year, fewest occur in the months of Decem- ber, January and February which are the coldest months in Ireland when temperatures may fall below zero.

Fleas are not active in cold weather. Ctenocephalides.canis, for example, has a strong disposition to spend the winter in the cocoon stage and flea eggs fail to hatch at low temperatures (Bacot, 1912). Cat, dog and human fleas occur on dogs in Ireland (Baker & Hatch, 1972). This is of some importance when considering control measures to be instituted. Cat, dog and human flea saliva has a common incomplete allergen (or hapten) so that a sensitized animal will react to the saliva of several species (Hudson et al., 1960).

Both Kissileff (1938) and Walton (1964) have demonstrated the characteristic pruritis and lesions which develop on dogs hypersensitive to fleas when fleas are released in their coats.

Clinical signs These are characterized by intense pruritus in areas of the body where fleas are

most often found (Figs 1-4). Affected dogs rub their backs under fixed objects or against walls and elicit a strong scratch reflex when the flanks are stroked with a finger. The primary lesion is a papule 1 cm in diameter, accompanied by erythema

3 20 K. P. B A K E R A N D J. O’FLANAGAN

of large areas of the dorsum. Secondary lesions result from self-excoriation with breaking of hair, local alopecia and, occasionally, areas of acute serous dermatitis. The characteristic distribution of the lesions is shown below (Fig. 1). Persistent excoriation over a period of many months in the untreated animal produces diffuse alopecia of the dorsum of the body with acanthosis and hyperkeratinization. Erythema is not noticeable at this stage and pruritus is less significant. Pruritus of the extremities, epihora, rhinitis and sneezing are not seen. These latter features distinguish the condition from other allergic diseases.

Ventral oreos Dorsal ore0

FIG. 1. Distribution of lesions of flea hypersensitivity.

Areas ofacuteserous dermatitis (‘wet eczema’) up to 10 cm in diameter may occur on any part of the body which can be reached by the tongue, teeth or feet. They are most common on the sites and the dorsum of the body but also occur on the head and neck. The areas are hyperaesthetic, soon become purulent and tend to heal quickly. Haemolytic, coagulase-positive staphylococci can often be isolated from these lesions, but it should be noted that these bacteria also occur on normal dog skin. In the sensitized dog, scratching results in renewed pruritus, a vicious circle results even though fleas are no longer present. This occurs in the sensitized human also, and immediate and delayed response may therefore occur. One of the authors (KB) experiences a delayed papular reaction (Hives) to injected flea saliva which wanes within 24 hours if not scratched; however, scratching at the sites of bites reactivates the tissue response, with further erythema and oedema, even though several days have passed since the initial challenge.

H Y P E R S E N S I T I V I T Y O F D O G S K I N T O F L E A S 32 1

FIG. 2. Alopecia, lumbo-sacral region.

Histopathology Skin biopsies were removed from clinical cases in the early acute and chronic

stages. The specimens were embedded in paraffin after fixing, sectioned and, after staining with haematoxylin and eosin, or toluidine blue, were examined under the microscope.

Early lesions show vascular dilation in the upper dermis, moderate acanthosis and upper dermal oedema. There is peri-appendageal and an upper dermal infiltration composed of lymphocytes, histiocytesj mast cells and polymorpho- nuclear leucocytes, with many eosinophils.

In the acute serous stage there is complete loss of the epidermis, upper dermal oedema, with marked upper dermal inflanimatory infiltration composed of neutrophils and eosinophils, the latter predominating. I n the chronic stage the epidermis is markedly thickened. There is extensive infiltration of the upper dermis by plasma cells, lymphocytes, neutrophils and mast cells, the eosinophil being the predominant cell. As in other stages there is vascular dilation.

Several authors have described the histopathological reactions to the bites of liaematophagous arthropods in sensitized animals. Rockwell & Johnson ( 1952) described dermal oedema with perivascular infiltration by polymorpho-nuclear leucocytes, eosinophils, lymphocytes and plasma cells in human beings sensitized to the bites of the mosquito Aedes aepypti. French & West (1971) report the reactions of the skin of sensitized guinea-pigs to the same parasite. Riek (1953a) in his extensive study of Queensland Itch of the horse, observed oedema of the dermis, with perivascular infiltration by eosinophils. Subsequently there was acanthosis.

C


FIG 3.

FIG. 4.

FIGS 3 and 4. Pustular dermatitis, or ‘wet eczema.’


Riek ( 1953a, b, 1954) submits considerable evidence which associates the disease with a hypersensitive reaction to the midge Culicoides robertsi.

It has been possible to sensitize guinea-pigs experimentally to the bites of the cat flea (Ctenocephalides felis fel is) (Larivee et al., 1964). A sequence of reactions was observed. I n the induction phase no microscopic changes were observed in the skin. With repeated exposure there was a subsequent delayed reaction with an intense mononuclear infiltration at the bite site, followed by an immediate reaction in which eosinophilic infiltration predominated, then a delayed reaction characterized by mononuclear infiltration. In the penultimate stage there was eosinophilic infiltration a t the bite site and then a stage of non-reactivity where no abnormality was observed in the dermis.

Diagnosis A diagnosis of flea allergy dermatitis can be made on the appearance of the

lesions, their distribution and the response to flea control. However, many owners have difficulty in accepting that socially unacceptable creatures like fleas are responsible for their pets’ skin lesions. An intradermal test may then be of value in indicating the association. I t is essential that corticosteroid therapy should be withdrawn 48 hours before the test. Unfortunately, depot corticosteroid therapy is widely used for the control of pruritis in dogs and will prevent any reaction to intradermal test solutions. Sufficient time should, therefore, be permitted to elapse after the use of this therapy for pruritus to redevelop before skin tests are attempted. Test solutions are not available commercially in the British Isles but may be prepared in the laboratory. Here the procedure is to grind whole washed fleas in a small volume of phenol saline. The mixture is then passed through a bacteriologi- cal filter and is ready for use (Baker, 1971). The technique is the introduction of the extract intradermally in the test subject. A portion of normal skin is chosen, this is clipped and cleaned with spirit, if necessary. Sufficient extract should be introduced to produce a bleb about 1 mm in diameter. It is most important that the injection be made intradermally and not subcutaneously. About 3 cm from this site a bleb of the vehicle for the allergen alone is introduced intradermally. A positive reaction is the production of a bleb 1 cm or more in diameter within 15 minutes at the extract site, no reaction having occurred at the control site.

The histopathology of tissue taken from a site of positive reaction is similar to that in the early papule of the field case.

Sertid (1965) reports 87 % positive reaction to intradermal flea allergens in dogs with clinical signs of flea allergy, dermatitis; Baker (1971) reports nearly 81 % positive reactions. Normal dogs show no reaction to the intradermal injection of whole flea extract (Baker, 1971).

Dzferential diagnosis In several diseases of dogs, pruritus occurs. Ectoparasites other than fleas may

provoke intense primary pruritus. The isolation of parasites with resolution after

324 K . P. B A K E R A N D J . O ’ F L A N A G A N

effective treatment with a parasiticide will eliminate this possibility. Food allergy is uncommon (Walton, 1967) and pruritus is usually present; there is, however, no characteristic distribution of areas where pruritus occurs. Allergy of this type may be accompanied by systemic disturbances which do not occur in flea hypersensitivity. Diagnosis of food allergy is most realiably made on the response to test meal investigations (Walton, 1967). There is no well-documented case record in the British Isles, of allergic reactions in dogs to inhaled allergens, though positive skin reactions to intradermal tests have been recorded (Baker, 197 1). Here again pruritus occurs but will be accompanied by epiphora, rhinitis and ‘nose-pawing’. Inhalent dermatitis is often seasonal and associated with maximum pollen release.

Pruritus may occur during the course of hepatic disease, diabetes mellitus and chronic nephritis ; therefore a thorough clinical examination, allied with the results of clinical pathological tests, should eliminate this group. Primary sensitiza- tion may follow the use of a particular dog shampoo; here the entire body is affected, and the reaction, though severe, is transient.

In flea alergy dermatitis the pruritic lesions have a characteristic distribution. The primary lesions are groups of papules with extensive erythema. These resemble the lesions of hives in man, most cases of which are in fact reactions to flea bites (Lunsford, 1949). Chronically affected cases show widespread alopecia of the back and marked thickening of the skin, with occasional abraided areas.

T R E A T M E N T

Corticosteroid therapy is widely used to control clinical signs of the disease. This merely masks the tissue reaction, and does nothing to remove the cause. I n addition, therapy must be maintained as long as fleas are active, which may be for the whole of the year in centrally-heated houses. Prolonged corticosteroid therapy is illogical and dangerous. A more rational treatment is the eradication of fleas from the environment. All animals which are potential hosts of fleas require dusting with a parasiticide. Eradication is feasible where contact with other hosts can be excluded; however, this will not often be possible.

The great majority of cases submitted to the clinic of the University of Dublin improve dramatically if adequate flea control is practised. hhl ler (1961) also reports successful treatment on strict flea control; 96% of his cases responded satisfactorily when fleas were eradicated from the animals’ environment. Collars impregnated with an organophosphorus insecticide may be worn : their drawback is that they do not immediately kill so that some biting occurs and reactions take place.

There is some evidence that hyposensitization using whole flea extracts for the production of blocking antibody r a y be successful for a period of some months without flea control (Keep & Taylor, 1967; Michaeli & Goldfarb, 1968). A study of the value of this method of therapy is being undertaken in this department.


D I S C U S S I O N

The reaction of human skin to biting parasites has been much studied (for example McKiel & West, 1961 ; Kilby & Silverman, 1967). These authors provide evidence that the mosquito bite reaction is an allergic response. Flea saliva contains an incomplete antigen requiring fixation with dermal collagen to be complete (Michaeli et al., 1965). Cross-reactivity between bites of C. felis, Pulex irrituns and Pulex simulans has been demonstrated in guinea-pigs by Hudson et al. (1960). I t can, therefore, be expected that a sensitized dog will react to the bites of fleas of several species. Experimental production of flea hypersensitivity in guinea-pigs shows a definite sequence of reaction beginning with a period of non-reactivity, followed by phases of different reactivity and terminating in a phase of non- reaction to flea bites (Benjamin et al., 1961). Definite histopathological changes are associated with the various phases (Larivee et al., 1964). Similar changes have been reported in man as a result of insect bites. It is considered that Queensland Itch (closely resembling ‘Sweet Itch’) is an allergic response of horses to the bites of the sandfly Culicoides robertsi.

There is considerable evidence that summer eczema (acute moist eczema, pyo- traumatic dermatitis) of dogs is also a hypersensitive reaction to biting insects. The distribution of the lesions corresponds to the areas where fleas are most often found: eradication of fleas from the environment of the affected animal results in resolution of the condition. The condition is seasonal and most cases occur during the warmer months of the year when fleas are most active. Exposure of sensitive dogs to the bites of fleas produces marked pruritus with the subsequent appearance of typical lesions (Kissileff, 1939 ; Walton, 1964).

That the clinical signs are not the mere result of the mechanical trauma of bites is indicated by the finding that, though most dogs are exposed to flea bites, only a comparatively small proportion react abnormally: also an induction period is required before the development of sensitivity. Some similarity to atopy is seen in the age for the development of clinical signs (Halliwell & Schwartzman, 1971). In both conditions very few cases occur in the first years of life, the majority commencing before the age of 5 years. Affected dogs have a high incidence of positive dermal reactions to flea extracts whilst normal dogs show no reaction. Further evidence for an antibody-antigen reaction is shown by the comparative success (though short term) of hyposensitization, using flea saliva or whole ground flea extracts. Possibly, hyposensitization occurs naturally in the persistently heavily infested dog in which clinical flea hypersensitivity is not seen. Though it has not been possible to demonstrate serum antibodies by agar plate gel diffusions tests (possibly because of their low concentration), evidence of circulating antibodies in dogs with flea hypersensitivity is shown by the positive reactions of the skin of normal dogs to whole flea extracts at the site of prior deposition of serum (72 hr) from clinically affected dogs (Baker & Quinn, unpublished). A similar positive reaction has been obtained by Hecht (1933) in a human patient sensitized to mosquito bites.


Though not similar, the skin reactions of dogs with flea hypersensitivity are comparable to those of man and experimental animals sensitive to insect bites. The histopathology of the positive dermal reaction to flea extract in dogs corresponds to that of the papule observed in the field case.

Several possible reactions of the skin to flea saliva may occur in dogs. I t is suggested that where massive persistent challenge occurs, the stages of induction, reaction and non-reaction are quickly passed through, whilst in some lightly infected dogs the period of induction is longer with the development of a hypersensitivity stage persisting for years.

A third group of moderately infested dogs show no reaction though challenged. I t can be shown that fleas have undoubtedly fed in this group by crushing them to release ingested blood. The great majority of dogs belong to this group. Why only a proportion of dogs react in an abnormal manner to flea saliva is not known. No studies have been undertaken to determine if there is a familial incidence of flea hypersensitivity in dogs as in atopy in man. A familial incidence might indicate an inborn abnormal reaction to the challenge of allergen(s) in flea saliva.

A C K N O W L E D G M E N T S

Thanks are due to the generous assistance given by the nursing staff of the clinic of the Faculty of Veterinary Medicine, University of Dublin.

R E F E R E N C E S

BACOT, A. (1912) Plague Supplement, 3. HTg. 12, 447. BAKER, K.P. (1971) 3. small Anim. Pract. 12, 445. BAKER, K.P. & HATCH, C. (1972) Vet. Rcc. 91, 151. BENJAMINI, E., FEINGOLD, B.F. & KARTMAN, L. (1960) ‘Nature 88, 959. BENJAMINI, E., FEINGOLD, B.F. & KARTMAN, L. (1961) Proceedings of the Societyfor Experimental

BENJAMINI, E., FEINGOLD, B.F., YOUNG, J.D., KARTMAN, L. & SHIMIZU, M. (1963) Exp. Parasitol.

FRENCH, F.E. & WEST, A S . (1971) 3. Parasitol. 57, 396. HALLIWELL, R.E.W. & SCHWARTZMAN, R.M. (1971) Vet. Rec. 89,209. HECHT, 0. (1933) zentralb1.f. Haul. 44, 241. HUDSON, B.W., FEINGOLD, B.F. & KARTMAN, L. (1960) Exp. Parasitol. 9, 18. KEEP, J.M. & TAYLOR, J.H. (1967) Awt. Vet. 3. 43, 425. KILBY, V.A. & SILVERMAN, P.H. (1967) Am. 3. Trop. Med. Hvg. 16, 374. KISSILEFF, A. (1938) 3. Am. Vet. Med. Ass., 93, 21. KISSILEFF, A. (1962) Small Animal Clin. 2, 132. LARIVEE, D.H., BENJAMINI, B.F., FEINGOLD, D.F. & SHLUIZU, M. (1964) Exp. Parasitol. 15, 491. LUNSFORD, C.J. (1949) Arch. Denn. CY Syph. 60, 1184. MCKIEL, J.H. & WEST, A S . (1961) PediatricClin. N. Am. 8, 785. MICHAELI, B. & GOLDFARB, A. (1968) Aust. Vet. 3. 44, 161. MICHAELI, D., BENJAMIN, E., DE BUREN, F.P., LARIVEE, D.H. & FEINGOLD, B.F. (1965) 3. Im-

Biology and Medicine 108, 70.

13, 143.

munol. 95, 162.

H Y P E R S E N S I T I V I T Y O F D O G S K I N 'ro F L E A S 327

MULLER, G.H. (1961) Small Animal Clin. 1, 85. MULLER, G.H. & KIRK, R.W. (1 969) Small Animal Dermatology. W. B. Saunders Co., Philadelphia. RIEK, R.F. (1953a) Aust. Vet. J . 29, 177. RIEK, R.F. (1953b) Aust. 3. Agric. Res. 5, 109. RIEK, R.F. (1954) A w l . V e t . 3 . 29, 177. ROCKWELL, E.J. & JOHNSON, F. (1952) 3. Invest. Dermat. 19, 137. SCHWARTZMAN, R.M. & ORKIN, M. (1962) A Comparative Study of Skin Disease of Dog and

Man. Charles C. Thomas, Illinois. SERTI~, V. (1965) Veterinarski archiv. (agreb. 35, 278. WALTON, G.S. (1964) Comparative Physiology and Pathology of the Skin, p. 561. (Eds Rook, A. &

Walton, G.S.) Blackwell, Oxford. WALTON, G.S. ( 1 967) Vet. Rec. 80, 709.

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Hypersensitivity of dog skin to fleas-a clinical report