Allergen immunotherapy in people, dogs, cats and horses - differences, similarities and research needs.

In human patients with seasonal allergic rhinoconjunctivitis sensitized to grass pollen, the first successful allergen immunotherapy (AIT) was reported in 1911. Today, immunotherapy is an accepted treatment for allergic asthma, allergic rhinitis and hypersensitivities to insect venom. AIT is also used for atopic dermatitis and recently for food allergy. Subcutaneous, epicutaneous, intralymphatic, oral and sublingual protocols of AIT exist. In animals, most data are available in dogs where subcutaneous AIT is an accepted treatment for atopic dermatitis. Initiating a regulatory response and a production of "blocking" IgG antibodies with AIT are similar mechanisms in human beings and dogs with allergic diseases. Although subcutaneous immunotherapy is used for atopic dermatitis in cats, data for its efficacy are sparse. There is some evidence for successful treatment of feline asthma with AIT. In horses, most studies evaluate the effect of AIT on insect hypersensitivity with conflicting results although promising pilot studies have demonstrated the prophylaxis of insect hypersensitivity with recombinant antigens of biting midges (Culicoides spp.). Optimizing AIT using allergoids, peptide immunotherapy, recombinant allergens and new adjuvants with the different administration types of allergen extracts will further improve compliance and efficacy of this proven treatment modality.

Prospective study of bacterial overgrowth syndrome in eight dogs.

Eight dogs with cutaneous lesions, clinical signs and cytological findings compatible with bacterial overgrowth syndrome were compared with four healthy dogs. The affected dogs were treated for 28 days with 30 mg/kg/day cephalexin. The results showed that the syndrome was a superficial cutaneous disorder characterised by marked pruritus, greasy seborrhoea, offensive odour, erythema, lichenification, hyperpigmentation, excoriations and alopecia involving principally the ventral aspect of the body, but no papules, pustules, epidermal collarettes or crusts; it was caused by overgrowths of Staphylococcus intermedius all over the body surface. Histopathological findings included a superficial, perivascular, hyperplastic and spongiotic dermatitis with a mixed inflammatory infiltrate, but no lesions suggestive of a true pyoderma. In the affected dogs, anti-staphylococcal immunoglobulin G levels were high, but anti-staphylococcal immunoglobulin E levels were low, suggesting that staphylococcal hypersensitivity is not the underlying pathogenic process. The antibiotic treatment improved the condition of all the dogs, but five of the eight had an underlying allergic skin disease.

The prevalence of immediate and delayed type hypersensitivity reactions to Microsporum canis antigens in cats.

Spontaneous recovery from Microsporum canis infections in cats is thought to be dependent on the development of a competent immune response. The purpose of this study was to determine the prevalence of positive delayed type hypersensitivity reactions in cats with and without dermatophytosis. Four groups of cats were intradermally skin tested with M canis extract and test sites were evaluated both subjectively and objectively at 0, 24 and 48 h after injection. Delayed intradermal testing (IDT) reactions were absent in cats not exposed to dermatophytosis (n=20); infected-recovered cats (n=38 culture negative lesion negative and n=43 lesion negative but culture positive) had significantly larger IDT reactions than unexposed cats and cats that were still actively infected (n=18). Based on the results of this study, IDT with M canis extract can be used to assess the cellular immune response of cats with dermatophytosis.

Parkinsonism in Ontario: physician utilization.

BACKGROUND: Patients with Parkinsonism have a progressive disorder requiring substantial expertise to manage effectively. METHODS: Over a six-year period we evaluated physician utilization and related costs for a large, unselected cohort of 15,304 Parkinsonian patients from the general population, comparing them to 30,608 age- and sex-matched controls within a universal health care system in Ontario, Canada. RESULTS: On average, 45% of Parkinsonian patients saw neurologists annually. The cumulative rate of at least one neurological consultation was only 59.5% over the six years. Patients aged < 65 had a much greater likelihood of consulting a neurologist (73.3%) compared to those > or = 65 (37.2%). Most Parkinsonian patients (97.2%), regardless of age, saw family physicians/general practitioners each year; 50.4% saw internal medicine consultants. CONCLUSIONS: Parkinsonian patients had increased likelihood of utilizing neurologists, primary care physicians and internists compared to controls; related costs of physicians' services were higher. Further research is necessary to evaluate differences in outcomes and costs between neurologists and other physician service providers.

IgE reactivity and cross-reactivity to Japanese cedar (Cryptomeria japonica) and cypress (Chamaecyparis obtusa) pollen allergens in dogs with atopic dermatitis.

The natural occurrence of Japanese cedar (Cryptomeria japonica) pollinosis has been reported in dogs with atopic dermatitis. However, the reactivity to Japanese cypress (Chamaecyparis obtusa) pollen allergens in these dogs has not been reported. The present study was designed to investigate the reactivity to Japanese cypress pollen allergens in dogs sensitized to Japanese cedar pollen allergens. In 19 dogs with specific IgE to C. japonica pollen allergen, we measured the specific IgE to C. obtusa pollen allergen and examined the reactivity to the allergen by intradermal test. Of the 19 dogs, 18 had specific IgE to crude and purified major allergens (Cha o 1) of C. obtusa pollen. Most of the dogs showed a positive reaction to C. obtusa pollen allergens in the intradermal test. Allergenic cross-reactivity between Cha o 1 and Cry j 1 (a major allergen in C. japonica pollen) was observed by the ELISA inhibition method. Dogs sensitized to Japanese cedar pollen allergens demonstrate reactivity to Japanese cypress pollen allergens.

The ACVD task force on canine atopic dermatitis (III): the role of antibodies in canine atopic dermatitis.

Although an important pathogenic role for IgE is established in the case of allergic asthma and rhinitis in man, its role in atopic dermatitis is less clear. There are many studies where allergists and immunologists have provided evidence in favour of such a role, whereas dermatologists are less than convinced. In dogs, however, there is an abundance of clinical evidence implying that atopic dermatitis is antigen driven, and recent studies suggest that there may be a role for IgE, not only in the effector pathway, but also in antigen capture. Although an IgG response often accompanies an IgE response in dogs with atopic dermatitis, there is little evidence in support of a pathogenic role in respect of the former isotype.

The ACVD task force on canine atopic dermatitis (IV): environmental allergens.

Numerous environmental allergens have been incriminated in the pathogenesis of canine atopic dermatitis (AD). These include dust and storage mite antigens, house dust, pollens from grasses, trees and weeds, mould spores, epidermal antigens, insect antigens, and miscellaneous antigens such as kapok. In this paper, we review the literature concerning the allergens that have been reported to contribute to canine AD. We conclude that attempts to identify the relevant canine antigens in the past have been plagued by a lack of standardisation of extracts and techniques, and the presence of false-positive and -negative reactions in allergy tests. Until these problems are rectified, it is unlikely that we will be able to provide a list of major and minor antigens for dogs. Hence, we recommend that future studies should be aimed at determining the major patterns of reactivity and cross-reactivity to specific protein allergens within antigenic extracts using electrophoresis and immunoblotting techniques. Once this information becomes available, it may be possible to use a selection of genetically engineered, highly pure antigens for both diagnostic and therapeutic purposes in canine allergy investigations. The use of such antigens will allow standardisation of canine allergy testing and immunotherapy so that the reliability and efficacy of these procedures can be objectively assessed.

The ACVD task force on canine atopic dermatitis (XII): the relationship of cutaneous infections to the pathogenesis and clinical course of canine atopic dermatitis.

Dogs and human beings with atopic dermatitis (AD) frequently exhibit concurrent skin infections with Staphylococcus sp. bacteria or Malassezia yeast, and treatment of such infections is an important facet of managing these patients. Staphylococci appear to colonize atopic skin readily, and bacterial products on the skin could augment cutaneous inflammation via immediate hypersensitivity responses to the bacteria, by superantigen-mediated lymphocyte activation, or other non-specific mechanisms. Similarly, skin colonization by Malassezia yeast could contribute to clinical signs of AD; yeast components could induce inflammation via non-specific mechanisms, such as alteration in mediator release, or via antigen-specific hypersensitivity reactions. Clinical and experimental evidence exists that secondary microbial infections can both initiate and perpetuate episodes of AD in dogs and humans, and could even participate in promotion of pro-allergic immunologic responses. Mechanistic details of these complex interactions are under extensive investigation in human beings; only a few observations have been extended to include dog with AD.

The ACVD task force on canine atopic dermatitis (XIV): clinical manifestations of canine atopic dermatitis.

Canine atopic diseases, including those with skin lesions, have been described for many years. Unfortunately, early descriptions often failed to establish definitive guidelines for considering a patient atopic, and criteria for diagnosing atopic dermatitis (AD) have varied from author to author. Larger case-series published from the 1960s to the 1980s suggested that the most common clinical manifestation of AD was pruritus, particularly of the face, ears, paws, extremities, and/or ventrum. It is not always clear that testing to eliminate other differential diagnoses was always carefully performed on patients in early reports; therefore, some descriptions could include patients affected with diseases other than or in addition to AD. Points of consensus regarding clinical manifestations of AD in case-series include the presence of pruritus beginning at a young age, possibly seasonally; and a prominent lesional involvement of the face, extremities, axillae or ventrum. Conflicting information on breed and sex predispositions is present, perhaps representing regional or temporal variability. Clinical reports vary, in regard to the description of lesions seen in dogs with AD. This reflects a possible confusion with lesions of secondary complications, and highlights the fact that the existence and nature of primary lesions of canine AD are not truly known.

The ACVD task force on canine atopic dermatitis (XV): fundamental concepts in clinical diagnosis.

The clinical signs of atopic dermatitis (AD) in man and in dogs are variable, and there is no single physical or historical feature that, if present, indicates the presence of AD. The initial diagnosis of AD is made clinically with the fulfillment of a combination of criteria that are strongly associated with the disease. Several schemes have been proposed in an attempt to define uniform clinical criteria for diagnosing canine AD, but no system is perfect. Once AD is considered as a possible diagnosis, other important differential diagnoses must be methodically eliminated from consideration. As a final step, once the clinician is certain that AD is probable, "allergy" tests may be conducted to provide additional evidence to "substantiate" the diagnosis. It is important to understand that allergy testing, in whatever form, is not appropriately used early in the patient evaluation as a screening test. Rather, it should be reserved, after a firm clinical diagnosis of AD has been made, to implement allergen avoidance schemes or to select allergens to be incorporated in immunotherapy formulations.

The ACVD task force on canine atopic dermatitis (XVI): laboratory evaluation of dogs with atopic dermatitis with serum-based "allergy" tests.

Serum-based in vitro "allergy tests" are commercially available to veterinarians, and are widely used in diagnostic evaluation of a canine atopic patient. Following initial clinical diagnosis, panels of allergen-specific IgE measurements may be performed in an attempt to identify to which allergens the atopic dog is hypersensitive. Methodology for these tests varies by laboratory; few critical studies have evaluated performance of these tests, and current inter-laboratory standardization and quality control measures are inadequate. Other areas where information is critically limited include the usefulness of these tests in diagnosis of food allergy, the effect of extrinsic factors such as season of the year on results, and the influence of corticosteroid treatment on test results. Allergen-specific IgE serological tests are never completely sensitive, nor completely specific. There is only partial correlation between the serum tests and intradermal testing; however, the significance of discrepant results is unknown and unstudied. Variation in test methodologies along with the absence of universal standardization and reporting procedures have created confusion, varying study results, and an inability to compare between studies performed by different investigators.

The ACVD task force on canine atopic dermatitis (XVII): intradermal testing.

Intradermal testing has been practiced for decades in human and veterinary medicine. The primary utility of intradermal testing is in the demonstration of IgE-mediated allergen hypersensitivity. The presence of a positive reaction on an intradermal test is not always indicative of allergy, as it may sometimes be an indication of sub-clinical hypersensitivity. Despite its widespread use by veterinary dermatologists, the usefulness of the intradermal test would be greatly enhanced by the use of standardized allergen extracts and homogeneous criteria for the interpretation of results. Irrespective of these shortcomings, intradermal testing is regarded as a valuable tool in the demonstration of allergen-specific hypersensitivity when performed according to accepted guidelines.

The ACVD task force on canine atopic dermatitis (XXI): antihistamine pharmacotherapy.

Antihistamines frequently are recommended by veterinary dermatologists for symptomatic treatment of pruritus associated with canine atopic dermatitis (AD), perhaps because of their moderate success in some human patients with AD. A critical review of the literature describing antihistamine use in canine AD reveals that the majority of published, peer-reviewed studies are open, uncontrolled or partially-controlled trials. Such studies vary widely in reported efficacy, from perhaps 0 to 75% of patients, even using the same drug. The few blinded placebo-controlled trials available have failed to confirm efficacy of these drugs to relieve the pruritus of canine AD. Some studies indicate that synergistic effects could occur with concurrent use of essential fatty acid supplements. Consequently, at the time of this writing, there is insufficient evidence to conclude for or against the efficacy of antihistamines for treatment of canine AD. Additional blinded, randomized and controlled trials with larger numbers of patients are necessary to establish which of the antihistamine drugs currently available, if any, are truly efficacious for canine AD. Nevertheless, present clinician consensus suggests that several different antihistamine drugs should be evaluated in sequence, for 7-14 days each, in canine patients with AD.

Commercial dry dog food in the north central United States is not contaminated by Dermatophagoides house dust mites.

Contamination of home-stored cereal grain food products with Dermatophagoides spp. house dust mites (HDM) was reported recently, along with anaphylaxis after consumption of these foods by dust mite-allergic people. We hypothesized that commercial dry dog food could become similarly contaminated, particularly if stored improperly, and could eventually contribute to allergic signs in dogs. Newly purchased bags of dry dog food (n = 30), from a variety of sources and manufacturers, and client samples of dry dog food (n = 50), stored under a variety of conditions, were obtained. Food samples were extracted in aqueous buffer, and extracts were assayed using ELISA for Dermatophagoides group II (Der II) allergen, as a marker for the presence of HDM. Der II allergen was not detected in any of the 30 newly purchased or 50 stored samples tested. Positive control samples consisting of house dust or dog food mixed with house dust, similarly extracted, and Dermatophagoides commercial allergen extract were positive for Der II in the same assay. We could find no evidence of HDM contamination in newly purchased or stored commercial dry dog food in the north central United States.

Analysis of the canine IgE-binding epitope on the major allergen (Cry j 1) of Japanese cedar pollen with anti-Cry j 1 monoclonal antibodies.

In our previous study [Immunology 91 (1997) 161] using monoclonal antibodies (mAbs) specific to Cry j 1, a major allergen in Japanese cedar (Cryptomeria japonica) pollen, we identified five independent epitopes (EP-1-EP-5) on the molecule and found that EP-1 and EP-5 are the predominant allergic epitopes for humans and monkeys, respectively. In this study, we analyzed the epitopes recognized by IgE in the sera of 10 dogs sensitive to C. japonica pollen allergen using an IgE-ELISA inhibition method with these mAbs. The IgE reaction patterns varied among dogs. In eight of the 10 dogs, IgE recognized EP-5 which is a predominant allergic epitope for monkeys with the pollenosis. In four dogs, IgE recognized EP-1 which is a predominant allergic epitope for human patients with the pollenosis. In three dogs, IgE recognized EP-4 which is a heat-stable epitope. EP-5 is a predominant allergic epitope for dogs and some, but not all, dogs have IgE reaction patterns to the epitopes similar to those of humans.

Parkinsonism in Ontario: increased mortality compared with controls in a large cohort study.

BACKGROUND: PD was associated with increased mortality before levodopa therapy became available. There have been conflicting reports of PD mortality in the modern era. OBJECTIVE: To assess current mortality rates in a large unselected population receiving treatment for parkinsonism (PKM) followed for up to 6 years. METHODS: Cases were identified using linked administrative databases, including physician service and prescription drug claims, generated in Ontario's universal health insurance system. Control subjects were identified from the provincial registry of citizens and age and sex matched to cases. Comparative mortality was evaluated over the 6-year period of the study (1993/94 to 1998/99). The sensitivity of the findings was tested with differing case definitions. RESULTS: In 1993, 15,304 patients with PKM were identified and were age and sex matched to 30,608 control subjects (1:2 ratio). Over the study period, 50.8% (7,779) of the cases with PKM died compared with 29.1% (8,899) of the control subjects. The cases with PKM had an overall mortality odds ratio of 2.5 (95% CI: 2.4, 2.6) compared with the control group. Results were consistent whether cases were defined by physician diagnosis, use of anti-PD drugs, or both criteria. CONCLUSION: Despite modern drug therapy, PKM continues to confer a sharply increased mortality on unselected patients followed for several years.

Bridging massive acetabular defects with the triflange cup: 2- to 9-year results.

An unresolved issue in total hip arthroplasty is acetabular reconstruction when there is bone loss that results in pelvic discontinuity, that involves radiation-compromised bone stock, or that is significant enough to exceed the limits of jumbo hemispherical cups. Achieving pain relief and initial and long-term implant stability on host bone are the major goals of this type of reconstruction. Seventy-eight hips in 76 patients in whom a large acetabular defect was bridged using a custom-designed, flanged component were reviewed retrospectively. The preoperative deficiency was classified as a combined deficiency in 39 hips and as a pelvic discontinuity in the other 39 hips. Six patients died before a minimum 2 years followup. With five patients considered lost to followup, there were 67 hips in 65 patients with an average followup of 53 months (range, 24-107 months). No Triflange Cup has been removed. Harris hip scores improved from a preoperative mean of 33.3 points to a postoperative mean of 82.1 points. Radiographically there are two patients with incompletely healed discontinuities but both are asymptomatic. Re-operation for recurrent dislocation occurred in six patients (7.8%). The Triflange Cup offers an alternative method of repair that reliably provides pain relief, initial implant stability, potential long-term implant stability, and pelvic stability in cases of discontinuity.

Experimental sensitization with Japanese cedar pollen in dogs.

Japanese cedar pollinosis is a type I allergic disease mediated by immunoglobulin E (IgE) antibodies to Japanese cedar (Cryptomeria japonica) pollen antigen (CPAg). By using 22 dogs consisting of 20 dogs aged 3 months and 2 dogs aged 3 years, immunization was performed by subcutaneous injections of CPAg with aluminum hydroxide gel. Variable levels of CPAg-specific IgE antibody response were detected in 21 of the 22 immunized dogs two weeks after the second immunization. This study provided an experimental sensitization system with CPAg in dogs, which will be useful for further immunological studies on Japanese cedar pollinosis.

Clinical experience with a modular noncemented femoral component in revision total hip arthroplasty: 4- to 7-year results.

A series of 163 revision total hip arthroplasties performed using a modular proximally porous-coated device was reviewed. Twenty patients died before achieving minimum follow-up, and 13 hips with Paprosky type IV femora were excluded. One patient was lost to follow-up. Minimum 4-year clinical data on the remaining 129 hips showed an improvement in modified Harris hip scores, from an average of 47.7 to 87.5. Spot welds at the sleeve-bone interface were found in 83 of the 102 hips with minimum radiographic follow-up. The aseptic failure rate was 2.9%; these hips showed progressive subsidence, with 1 resulting in the only repeat revision in the series. Three hips had osteolytic lesions of <5 mm; none threatened implant stability. There were no complications related to modularity.