Sweet Itch Research Articles

Characterisation of lymphocyte subpopulations in the skin and circulation of horses with sweet itch (Culicoides hypersensitivity).

Circulating lymphocyte numbers are elevated in horses with the allergic skin disease sweet itch and skin lesions are typified by an infiltrate of eosinophils and mononuclear cells, the latter of which have not been fully characterised. The aim of the present study was to characterise the lymphocyte subpopulations in the circulation and skin of ponies with sweet itch by flow cytometry and a newly developed modified alkaline phosphatase immunohistochemical technique. Sweet itch ponies were found to have significantly greater numbers of circulating CD5+ and CD4+ T-lymphocytes than normal animals. Increased numbers of CD3+ T-lymphocytes, most of which were CD4+, and eosinophils were present in the skin of these animals following intradermal injection of a Culicoides antigen extract (97 +/- 21 vs. 449 +/- 49 CD3+ T-lymphocytes/mm2 in deep dermis of vehicle vs. antigen injected sites; 83 +/- 8% CD4+ T-lymphocytes at antigen injected site). T-lymphocytes, which are thought to be important in the pathogenesis of human allergic skin disease, may therefore contribute to the development of sweet itch lesions via the release of cytokines which can cause eosinophil accumulation and activation. An understanding of the pathology of this disease may lead to a more rational approach to therapy.

Treatment of Equine Allergic Diseases with Allergy Neutralization. A Field Study

The allergy desensitization technique, known as intradermal neutralization, was originally described by Dr H. Carlton-Lee. The procedure was later extended and modified by Professor J. B. Miller of Mobile, Alabama and currently is used extensively for treating allergic disease in humans, especially in the USA, but also in Canada, the UK and Australia. The technique has been shown in many clinical papers to be effective in humans as a means of desensitizing both food and biological inhalant allergens. It is also effective in chemical sensitivity. Although there have been sporadic reports of successful use in horses and other animals, this is the first to show a marked effect in equine asthma, otherwise known as chronic obstructive pulmonary disease or heaves. The results in equine urticaria are even better and there appears to be benefit in some cases of headshaking (equine rhinitis). The number of horses treated for sweet itch was too small to draw any conclusion. The positive effects shown in this stud...

Agonist-induced adherence of equine eosinophils to fibronectin.

Eosinophils are believed to play an important part in the pathogenesis of equine diseases such as helminth infestation and the allergic skin disease, sweet itch. It has been shown that adherence of human eosinophils to the connective tissue matrix protein fibronectin enhances cell activation and survival time. If adherence causes similar changes in the properties of equine eosinophils, cell-induced tissue damage at a site of parasitic infestation or allergic response would be exacerbated. However, investigation of this hypothesis requires identification of mediators that cause equine eosinophil adherence. Since the equivalent recombinant equine proteins were not available, the present study reports the effects of recombinant human (rh) C5a and IL-5 on the adherence of equine peripheral blood eosinophils (EPBEs) to fibronectin in vitro. The effects of LTB4 and PAF on EPBE adherence to fibronectin were also examined and phorbol myristate acetate (PMA) was used as a positive control. PMA caused a dose-related increase in EPBE adherence to fibronectin-coated plastic. In comparison, rh C5a produced a much smaller response which was only evident at the highest dose tested. On the other hand, rhIL-5 induced a small, but significant dose-related increase in EPBE adherence. Moreover, this response was in part dependent on the beta 1 integrin Very Late Antigen-4 (VLA4). Since adherence to serum-coated plastic was also increased by IL-5, beta 2 integrins may be activated and/or up-regulated on EPBEs by the cytokine. Neither LTB4 nor PAF caused EPBE adherence to fibronectin but prior incubation with these mediators increased the response of cells to IL-5. There were no differences between the responses of EPBEs isolated from horses with clinical signs of sweet itch and normal animals. Thus, whilst up-regulation of IL-5-induced adherence may occur locally in tissues in vivo, it does not appear to take place in the circulation. Finally, C5a, PAF and LTB4, but not IL-5, caused equine neutrophil adherence to fibronectin demonstrating the different responses of granulocytes to these mediators. The results obtained in the present study have shown that mediators which may be released at sites of inflammatory or allergic reactions can induce or enhance eosinophil adherence to tissue matrix protein. Thus, these mediators can now be used in future studies to determine if cell adherence may alter eosinophil activation or survival time.

Actions of PAF receptor antagonists in horses with the allergic skin disease sweet itch.

Platelet activating factor (PAF) mimics the effects of Culicoides antigen by inducing oedema and inflammatory cell accumulation in the dermis of horses with the allergic skin disease, sweet itch. PAF could therefore contribute to antigen-induced inflammatory changes in these horses. We now report that intravenous administration of the PAF receptor antagonist WEB 2086 (3 mg kg-1), at a dose that inhibited the vascular and cellular responses to PAF in sweet itch horses, reduced Culicoides antigen-induced oedema at 1 h by 73% and at 8 h by 71% (p < 0.05). Neutrophil accumulation and eosinophil recruitment were not significantly reduced by WEB 2086 or a second hetrazepine PAF receptor antagonist WEB 2170 (0.1 mg kg-1). These findings suggest a key role for PAF in oedema formation, but not inflammatory cell accumulation, induced by Culicoides antigen in the skin of sweet itch horses.

Platelet activating factor mimics antigen-induced cutaneous inflammatory responses in sweet itch horses

Hypersensitivity responses to biting flies such as Culicoides are believed to be the cause of sweet itch, a seasonal intensely pruritic skin condition of horses. Little is known about the mediators released by antigen in the skin of affected horses. In the present study the cutaneous vascular and cellular responses to intradermally injected platelet activating factor (PAF) have been characterised in sweet itch cases during the active phase of the disease and compared with those of Culicoides antigen extract. Histamine was used as a positive control in vascular permeability studies. Responses were also examined in 4 of the 5 sweet itch cases during the inactive phase of the disease. Normal ponies were used as controls. PAF-induced increases in vascular permeability that were dose-related (0.001–1 μg per site) and of a similar magnitude in sweet itch and normal animals. Antigen (0.5–50 μg per site) also caused dose-related wheal formation in sweet itch cases during the active, but not the inactive, phase of the disease. This effect was biphasic, with maximal responses occurring at 1 and 8 h. An increase in vascular permeability occurred in normal ponies only after administration of the highest dose of antigen tested. Interestingly, histamine (0.02 μg per site) induced wheals were significantly smaller in the affected, compared with the normal, group, both during the active and inactive phases. PAF and antigen caused neutrophil accumulation in the skin of sweet itch and normal animals during both the active and inactive phases of the disease. Eosinophil recruitment was also observed but only in the affected group and, in the case of PAF, during the active, but not the inactive, phase. Antigen additionally caused the accumulation of mononuclear cells in the skin of sweet itch cases during the active phase, PAF induced a small increase in mononuclear cell numbers in these animals but the increase was not statistically significant. These findings demonstrate that PAF mimics the effects of Culicoides antigen during the active phase of the disease. Hence, PAF, like histamine, may play a role in the pathogenesis of antigen-induced responses in the skin of sweet itch horses.

PAF- and LTB4-induced migration of eosinophils and neutrophils isolated from horses with allergic skin disease

Platelet activating factor (PAF) and leukotriene (LT)B4 cause thein vitro migration of equine granulocytes. In this study eosinophils and neutrophils have been prepared from horses showing clinical signs of the allergic skin disease sweet itch. Migratory responses have been compared to those of cells from normal animals. Cell migration was measured in a 48-well microchemotaxis chamber. PAF and LTB4 caused the migration of neutrophils and eosinophils from both allergic and normal horses. However, responses of eosinophils, but not neutrophils, from allergic horses were significantly reduced (p<0.05,n=5). No difference was observed between the random movement of neutrophils or eosinophils from normal and allergic horses. These results suggest that the migratory responses to PAF and LTB4 of eosinophils from allergic horses are down-regulated.

Immunopathological study on equine insect hypersensitivity (“kasen”) in Japan

Equine "kasen" is a chronic dermatitis that occurs especially during the summer months. In the present study, skin lesions of kasen that were collected by biopsy from May to October were classified histopathologically into three stages: initial (Group I, 30 cases), developing (Group II, 48 cases) and regressing (Group III, 13 cases). The characteristic lesions were hyperkeratosis, an increase in the number of T-lymphocytes and Langerhans cells (positive for class II MHC) at the epidermo-dermal junction, oedema of the dermis and perivascular infiltration of eosinophils and mast cells. Ultrastructurally, numerous Birbeck granules were observed in the cytoplasm of Langerhans cells. These lesions were striking in Group II and less so in Group III. Kasen is therefore considered to be similar to Queensland itch and sweet itch as described in Australia and Britain, respectively. The histological features were characteristic of a type I and type IV allergic dermatitis.

Immunogenicity and Allergenicity of Culicoides imicola (Diptera: Ceratopogonidae) Extracts

Summer seasonal recurrent dermatitis (SSRD) or "sweet itch" is a seasonally occurring allergic dermatitis of horses provoked by biting midges. The allergic skin reactions have been attributed to allergens present in various Culicoides species. C. imicola is the suspected etiological agent of SSRD in Israel. Whole body extracts of this midge induced hypersensitivity reactions upon injection into susceptible horses and in this study attempts were made to define components of C. imicola which have immunogenic and allergenic properties. Immunogenic potency was evaluated by raising antisera to whole body extracts of C. imicola in rabbits and examining their reactivity towards fractionated extracts. Allergenic potency was examined by reacting fractionated extracts with horse sera. Humoral reactivity of susceptible and non susceptible horses was assayed by specific IgE and IgG ELISAs. Although there are many antigenic components in whole body extracts of C.imicola capable of eliciting an immune response, no conclusive evidence was obtained indicating that allergic reactivity was associated with increased IgE levels of defined specificity.

Potential of infra-red thermography for the detection of summer seasonal recurrent dermatitis (sweet itch) in horses.

The feasibility of using infra-red thermography for early and out of season detection of summer seasonal recurrent dermatitis (sweet itch) was tested on 13 sensitive and six insensitive horses in Israel. In summer (June, July and September) six affected mares and two unaffected sensitive mares (one of them a pony) were clearly 'warmer' in the affected zones than three insensitive mares. In winter (February and March) unaffected sensitive horses could be differentiated from insensitive mares by the warm areas detected in the affected zones. Small numbers of Culicoides imicola bites may have been the cause of the local heat reactions of the body that were detected by the infra-red radiometer.

Preferred landing sites of Culicoides species (Diptera: Ceratopogonidae) on a horse in Israel and its relevance to summer seasonal recurrent dermatitis (sweet itch)

Six hundred and twenty culicoides of five species were collected from a bait horse at Kannot, Israel, between April and September 1986. Seventy-two per cent of the midges were collected from the belly and 27 per cent from the dorsal aspect of the body, ie, the sweet itch summer seasonal recurrent dermatitis (SSRD) zone. Midges were active mainly from half an hour prior to half an hour after sunset. Only Culicoides puncticollis, C imicola and C schultzei group were collected in considerable numbers. While C imicola was present continuously throughout the season, the appearance of the two other species was intermittent. Ninety-five per cent of C schultzei group and approximately 100 per cent of the C puncticollis prefer to land on and most probably bite the belly. Culicoides imicola showed a clear preference for the dorsal ridge which overlaps the (SSRD) itch zone, and 70 per cent of the midges were collected there, while 28 per cent were collected from the belly. A considerably high proportion of the midges of this species were parous, ie, part of the population lived long enough to bite more than once. Skin temperature measurements showed the belly to be the warmest part of the body. Wind speeds of two to three knots reduced the number of midges collected. The findings of this study, together with a previous one (Braverman et al 1983), incriminate C imicola as the likely principal agent of SSRD in Israel.

Seasonal allergic dermatitis in sheep.

The lesions of a seasonal dermatitis in sheep occurred mainly on the ventral surface of the animals, but in other respects they resembled those of 'sweet itch' in horses. They were primarily an immediate hypersensitivity response and the circumstantial evidence indicated that they were due to the bites of Culicoides species, possibly C obsoletus.

High-cis permethrin for the control of sweet itch on horses.

High-cis permethrin for the control of sweet itch on horses.

Allergic dermatitis (sweet itch) of Icelandic horses in Sweden: an epidemiological study.

A survey of allergic dermatitis (sweet itch) in Sweden contained information on 441 Icelandic horses. Results of a questionnaire indicated that approximately 15 per cent of the country's Icelandic horses suffered from the disease. The prevalence of allergic dermatitis was significantly higher among horses imported from Iceland (26.2 per cent) compared to that of Swedish-born animals (6.7 per cent). In addition, horses born in Iceland were significantly more severely affected than horses born in Sweden. The risk of allergic dermatitis in Sweden appeared to be more than six times higher for horses exported from Iceland to Sweden relative to that of horses originally born in Sweden. The prevalence of disease for horses of seven years or older was 30 per cent for Icelandic-born individuals as compared to 7.3 per cent for horses born in Sweden. Similarly, the risk of allergic dermatitis in Sweden for horses of seven years or older appeared to be nearly 10 times higher for horses imported from Iceland relative to that of horses born in Sweden. Allergic dermatitis usually appeared during the third grazing season for imported horses and during the fourth season for horses born in Sweden. Furthermore, the course of the disease tended to become worse with time. Analysis of the prevalence of allergic dermatitis relative to gender revealed no significant differences. Certain geographical variations in the prevalence of the disease was also found.

Skin Lesions of Sweet Itch and the Distribution of Dermal Mast Cells in the Horse

SummaryIntradermal skin tests using insect allergens were carried out in different regions of two horses; a horse with sweet itch and a clinically normal horse. There was greater variation in the response at challenge sites on the horse with sweet itch than on the normal horse. Mast cell counts were performed on skin samples taken from a number of regions of seven horses. While these cells tended to be more numerous along the dorsal mid‐line no clear pattern emerged which could be associated with the distribution of lesions in sweet itch. Mast cells tended to be more numerous in horses less than one year old.ZusammenfassungHautläsionen bei Sommer‐Dermatitis und die Verteilung dermaler Mastzellen beim PferdIntradermale Hauttests mit Insektenallergenen wurden an verschiedenen Hautregionen von 2 Pferden durchgeführt, bei einem Tier mit Sommer‐Dermatitis und einem klinisch gesunden Tier. Es waren größere Unterschiede in der Hautreaktion an den Teststellen bei dem Tier mit Sommer‐Dermatitis verglichen mit dem gesunden Tier festzustellen.Bestimmungen der Zahl der Mastzellen wurden anhand von Hautproben von verschiedenen Hautarealen bei 7 Pferden vorgenommen. Obwohl diese Zellart häufiger entlang der dorsalen Mittellinie vorzukommen scheint, war kein deutliches Verteilungsmuster in Verbindung mit dem Auftreten der Läsionen bei der Sommer‐Dermatitis festzustellen. Mastzellen waren bei Pferden im Alter unter 1 Jahr zahlreicher anzutreffen.

Some characteristics of the antibodies involved in allergic skin reactions of the horse to biting insects

Active skin tests were carried out on a horse with sweet itch using extracts of various biting insects and the resulting reactions compared with those produced when rabbit anti-human IgE was injected intradermally into a normal horse. The horse with sweet itch produced a large reaction to an extract of Culicoides which was similar to those produced by anti-human IgE. Absorption of serum from an allergic horse with anti-human IgE reduced its ability to sensitize skin of a normal horse to challenge with the extract of Culicoides. Passive transfer of allergic horse serum to guinea-pig skin gave significant reactions when challenged after a latent period of 4 h but not after 24 h.

Treatment of equine onchocerciasis with ivermectin paste.

A single oral dose of ivermectin paste was administered to 12 horses with dermatitis and clinical signs typical of onchocerciasis. Two of the horses also had lesions of Queensland itch. Microfilarias of Onchocerca cervicalis were identified in fresh, macerated, skin biopsies from the neck, brisket or umbilical regions of all horses and microfilarias of O. gutturosa from the neck of 2. Eight of the horses developed skin reactions 4 to 24 h after the administration of the ivermectin, notably weals over the neck, shoulders and flanks and pitting oedema of the ventral midline and intermandibular space. Regression of the onchocerciasis lesions was evident within 7 days of treatment and affected skin had returned to normal within 3 months. The lesions of Queensland itch were not affected by the ivermectin treatment. Microfilarias were present in biopsies of skin, particularly in the superficial dermis, before treatment, but were absent from all skin biopsies taken one week after treatment. In some horses transient skin sensitivity reactions developed. Microfilarias began to reappear in the biopsies of some of the horses 2 months after treatment. It is concluded that the oral paste formulation of ivermectin, although not effective against adult onchocerca, is useful for the therapeutic control of microfilarias in the skin lesions of equine onchocerciasis.

Biting midges (Diptera: Ceratopogonidae) as vectors of nonviral animal pathogens.

A review is presented of the animal parasites (other than viruses) that are transmitted by Ceratopogonidae. The organisms involved (12 Protozoa, 18 Nematoda) are tabulated with their respective natural and experimental vectors. Tabulated summary data dealing with developmental characteristics of the parasites in their insect hosts are also given. The skin condition of horses known as “sweet itch” or “Queensland itch” is reviewed briefly.

A disease resembling sweet itch in Hong Kong.

A disease resembling sweet itch in Hong Kong.

Preferential landing and engorging sites of Culicoides species landing on a horse in Ireland.

An investigation of the landing and engorging sites of midges on a bait horse was made in Ireland as part of a project examining the aetiology of sweet itch. Ten species were recovered, seven of which engorged. Culicoides obsoletus and C dewulfi were the most commonly represented, accounting for 89.9 per cent of midges landing and 90.5 per cent of midges engorging. Only 4.69 per cent of midges attracted to the bait were C pulicaris. Overall, the preferential landing sites for midges were along the mane and lower leg regions. Few culicoides were attracted to the head, front and underside of the animal. Two species, C punctatus and C nubeculosus, fed exclusively at the predilection sites of sweet itch but in very small numbers. C pulicaris fed predominantly at these sites also and represented 5.08 per cent of the engorging catch. Of 10,178 midges attracted to the bait, 4097 (40.3 per cent) engorged; the majority of the species taking full blood meals fed on the mane and lower legs. Midges biting in other areas tended to have smaller meals. Areas along the dorsal midline of the body are predilection sites for sweet itch lesions and are preferential engorging sites also. However, considerable engorgement occurred on the lower legs where sweet itch lesions do not occur.

A reagin-like antibody in horse serum: 1. Occurrence and some biological properties.

The demonstration of a reagin-like antibody against Culicoides pulicaris extract in the serum of horses and ponies affected with recurrent seasonal dermatitis (sweet itch) is reported. This antibody can confer Prauznitz-Küstner (P-K) sensitivity on homologous skin for up to 5 days and, like human IgE, is thermolabile and susceptible to 2-mercaptoethanol reduction. It is eluted on diethylaminoethyl dextran-52 anion exchange chromatography independently of IgG, IgG(T) and IgM, and its elution characteristics indicate similarity in net molecular charge to human IgE. The P-K response observed in horse skin is biphasic, and is morphologically similar to the late cutaneous anaphylactic response in man. Both phases of the P-K response are dependent upon the reagin-like antibody, although other serum factors appear involved in the delayed phase of the response.