Allergens are antigens that cause type 1 hypersensitivity reactions, and an allergy is an exaggerated response to this stimulus. Over-reaction to antigen stimulation can manifest itself in an animal's skin. All pets can be affected to some extent by flea and fly bites, but an allergic pet will react with disproportionate severity, causing just a few bites to significantly harm the skin. The hyper-sensitivity is a physiological aberration where the host's immune system erroneously recognises a nontoxic foreign substance that has entered the body as harmful. In an effort to combat the substance, called an allergen, the animal's immune system releases a chemical compound called histamine. The eagerness to scratch characteristically suggests the presence of a flea or fly bite allergy, and is often accompanied by dermatitis. The most common skin allergy encountered in small animal veterinary medicine is flea bite hypersensitivity, also known as flea allergy dermatitis (FAD). FAD can often coexist with other allergic conditions such as atopic dermatitis. This disease exhibits pruritic dermatitis in animals that have become sensitised to antigenic material in flea saliva. However, dogs exposed to flea burdens on a continuous basis may become partially or completely immuno-tolerant and this condition may be broken when dogs are exposed in an intermittent manner (Wilkerson et al, 2004). Flea infestations also lead to human irritation and flea bite reactions, as well as eroding the human–animal bond. As a result, flea control should be considered part of a ‘one health’ approach, improving human wellbeing with flea control, as well as the well-being of the pet. Desire and medical necessity to control fleas has led to more than $1 billion in the USA, and €1.1 billion in Europe, being spent on companion animal flea control annually (Rust, 2005). Similarly, fly bite sensitivity in horses caused by Culicoides spp. is a common cause of dermatitis, unofficial recording by organisations such as the national sweet itch society suggest 3–5% of horses in the UK may be affected but there is no official figure and this may be an underestimate.
As well as being a source of FAD, fleas are also a public health issue. They can transmit pathogenic agents such as the tapeworm, Hymenolepis nana, and bacterial diseases like salmonellosis, tularaemia, murine typhus and the bubonic plague. Fleas are also an intermediate host of the flea tapeworm, Dipylidium caninum.
Flea bite hypersensitivity
This disease has a simple pathophysiology (Figure 1). Once the flea starts feeding, the flea's saliva compounds act as proteinic antigens or haptens (incomplete antigens), which when combined with the dermis' collagen, turn into allergenic antigens. The flea's saliva contains a number of substances that can be potentially irritant or allergenic such as polypeptides, amino acids, aromatic compounds and fluorescent materials. Then, the Langerhans cells capture them and migrate through the blood vessels to the nearest lymphatic nodes, and the complete antigen is presented to T lymphocytes. These are then activated and recruit the T helper 2 (Th2) cells to produce immunoglobulin E (Ig E) by B lymphocytes, which sensitise mast cells in order to release substances like histamine. These substances provoke discomfort and pruritus, leading to self-inflicted traumas with subsequent bacterial infections. In chronic cases, thickening and hyperpigmentation of the skin can be seen. In the first blood meal, no immunological reaction is present, but the animal is then sensitised to subsequent bites. The allergic reaction can occur 15 minutes after the blood meal (type I), or 14–48 hours later (type IV). In hypersensitive animals, just a single blood meal can trigger severe allergic reactions. This demonstrates that the degree of irritation is directly proportional to the degree of hypersensitivity, which varies from animal to animal. However, it has been demonstrated that a continuous exposure to fleas, from an early age, tends to predispose animals to a form of hyposensitivity (Tizard, 2002).

Clinical examination and assessment of clinical signs
In order to better assess these lesions, a scoring system would be advised to better quantify erythema, papules, crusts, scale, alopecia and excoriation, grading each lesion as follows:
Three body sites should be included in every patient with a flea infestation history:
Modelling studies of FAD have shown that dogs exposed episodically, rather than on a continuous basis, show dermatologic lesions much quicker. They can appear as soon as the second day of flea exposure, whereas those exposed continuously did not show lesions until day 16 (Wilkerson et al, 2004). Signs can range from mild erythema to severe bacterial infections (Figure 2) owing to the pruritus, and discomfort it causes. Use of scoring systems such as the one described above allows veterinary nurses to assess response to treatment and progression of disease, even if a number of different veterinary professionals have seen and treated the patient over a period of time.

Diagnosis
Clinical presentation will alert veterinary professionals to the possibility of FAD, and nurses may find typical clinical signs in nurse flea clinics. Also, it is known that some breeds are more prone to develop FAD, such as the German Shepherd, whereas West Highland White Terriers and Chinese Shar-Peis are less prone. Another point to remember is that this condition is usually more prevalent in young adults. The most common conditions involved in the differential diagnosis are food allergies, atopic dermatitis, dermatophytosis, demodicosis, superficial pyoderma and other parasitic dermatoses such as lice and cheyletiellosis (Blagburn and Dryden, 2009). The presence of fleas and/or flea dirt on combing (Figure 3), relevant clinical signs, and the presence of Dypilidium caninum segments in the faeces or crawling around the anus, are all highly suggestive of FAD. It is useful if clients are advised not to wash pets before appointments as fleas and flea dirt may be removed. Resolution of clinical signs with adequate flea control may be sufficient to conclude that FAD is the source of presenting clinical signs, but allergy blood testing or intradermal tests are required to confirm a diagnosis. A positive reaction, however, only implies the presence of IgE against flea allergens, and does not on its own confirm that FAD is the cause of the clinical signs being investigated. It is important to correlate results with response to flea control and the overall clinical history. Dietary trials with exclusion diets can also be used to rule out concurrent food allergies.

Treatment and control
Aggressive flea control is the principal means of treating FAD, and may be the only treatment required. The success to control pet flea infestations includes a combination of strategies. These include treatment of the environment with insecticides and insect growth regulators such as pyriproxyfen and lufenuron. These can be applied to the environment as sprays or as part of spot-on preparations that are subsequently shed into the environment. Lufenuron is administered systemically, preventing eggs from feeding fleas hatching.
Silicone sprays and daily vacuuming have also been shown to have some effect on environmental life stage numbers. To achieve control, all adult cats, dogs, rabbits and ferrets in the household must be treated for at least 3 months with an adulticide that will kill all adult fleas within 24 hours of feeding (Dryden et al, 2000). Clinically affected pets should be treated with an adulticide that will kill fleas as quickly as possible without compromising compliance to limit feeding (Rust, 2005).
Nurses play a vital role in establishing history of flea treatment, animals present in the household, administration likely to maximise compliance, and lifestyle of the pets. It is also important that nurses demonstrate how to accurately apply flea treatments, and emphasise the length of time that will be required to bring flea infestations under control. Nurses can also show clients how to perform flea dirt checks with damp cotton wool, as well as how to use a flea comb at home to monitor efficacy of control and reduction of flea numbers. By maximising compliance and limiting expectation for rapid elimination, compliance and the likelihood of flea control is increased. To decrease inflammation and pruritus while flea control is achieved, anti-inflammatory doses of corticosteroids may be required, as well as control of secondary bacterial and yeast infections. In dogs, oclacitinib maleate (Apoquel®, Zoetis) may be used to control pruritus.
Fly bite hypersensitivity
Clinical examination and assessment of clinical signs
Cats and dogs can also develop allergen-specific IgE to a variety of insects. The relationship between these reactions and allergic dermatitis, however, is still unclear. It should be considered in dermatitis cases that are negative for other allergens on intradermal testing and allergy blood testing, but are responsive to anti-inflammatory and anti-pruritic drugs. In horses, clinical signs are associated with the areas of the body where Culicoides spp. midges feed. Dermatitis and intense pruritus occurs dorsally (mane, lateral neck, shoulders, withers, rump and tail), or ventrally (face, ears, chest ventral abdomen and groin).
Diagnosis
In cats and dogs, diagnosis is one of exclusion, as biting insects other than fleas are not included on allergy blood test and intradermal testing panels. Parasitic infection, dermatophytosis and primary yeast infections should be eliminated through tape strips, skin scrapings and possibly cultures. If these can be eliminated as possibilities and patients respond to anti-inflammatory/anti-pruritic agents, fly bite sensitivities become more likely. An accurate clinical history is important where fly bite sensitivity is suspected to see if pets frequent areas where fly bites are likely to be intensive and frequent, such as rural areas, stables or fields containing livestock. In horses, clinical history is vital to ascertain if Culicoides spp. bite sensitivity (‘sweet itch’) is likely to be a cause of dermatitis. Clinical signs typically occur in the summer months when Culicoides midges are active. Young horses are most commonly affected, although signs may occur in horses of any age. Differential diagnoses that should be considered are other ectoparasites, food reactions and pinworm if lesions are limited to the rump and tail. These other sources of reaction tend to be non-seasonal in nature, but ectoparasites should still be eliminated through combing, hair plucks for ectoparasites, and peri-anal tape stripping for pinworm eggs.
Treatment and control
Where fly bite sensitivity is suspected, efforts should be made to keep pets indoors or away from high-risk areas. If it is not practical or desirable to achieve this, fly repellents are an alternative. In dogs, permethrin spot on preparations, a deltamethrin or flumethrin collar may be employed. In cats, pyrethroids are contraindicated because of toxicity risks. The exception is a flumethrin collar (Seresto®, Bayer), which is likely to have some useful fly repellent efficacy in cats and is safe for use. Glucocorticoids may be required to control inflammation, antibiotics and antifungals for secondary infection, and Apoquel® (Zoetis) in dogs to control pruritus. Similarly, in horses, pyrethroids applied topically are useful, with permethrin and cypermethrin having demonstrated some efficacy (Papadopoulos et al, 2010).
Breathable whole-body blankets that are impregnable to midges may also be employed. Glucocorticoids are the mainstay of anti-inflammatory and anti-pruritic treatment to control immediate clinical signs. Bathing can also help as cool water causes peripheral constriction to limit inflammatory mediators, mini-mises percutaneous absorption of allergens, and rehydrates the skin. Nurses play an important role in discussing and demonstrating control options to clients, and establishing which is best likely to work in the individual patient.
Conclusions
Fleas and flies are important causes of primary skin disease in dogs, cats and horses. Compliant use of host-targeted flea-and fly-control products, together with knowledge of flea-and fly-life cycles, is necessary to control fleas and flies on the animal, in the home, and in outdoor environments. Nurses play an important role in establishing whether or not exposure to biting insects is occurring, and developing effective control strategies with the client.