Allergen-specific IgG antibodies in cats with allergic skin disease

An enzyme-linked immunosorbent assay was developed for quantifying feline serum allergen-specific IgG directed against selected house dust, pollen and flea allergens. The assay was used to compare allergen-specific IgG concentrations in sera from healthy cats, cats with non-dermatologic illness, confirmed allergic cats and undiagnosed pruritic cats. Our results demonstrate that cats with confirmed allergic skin disease have significantly more IgG directed against house dust, flea and ryegrass allergens than other cat groups examined. These results support the theory that cats with allergic skin disease have an underlying T_H2 lymphocyte response that directs production of both allergen-specific IgG and IgE.     

Factors affecting allergen-specific IgE serum levels in cats

Pruritic skin diseases are common in cats and demand rigorous diagnostic workup for finding an underlying etiology. Measurement of a serum allergen-specific IgE in a pruritic cat is often used to make or confirm the diagnosis of a skin hypersensitivity disease, although current evidence suggests that elevated allergen-specific IgE do not always correlate with a clinical disease and vice versa. The aim of the study was to to assess the possible influence of age, deworming status, lifestyle, flea treatment, and gender on allergen-specific IgE levels and to evaluate the reliability of IgE testing in predicting the final diagnosis of a pruritic cat. For this purpose sera of 179 cats with pruritus of different causes and 20 healthy cats were evaluated for allergen-specific IgE against environmental, food and flea allergens using the Fc-epsilon receptor based enzyme-linked immunosorbent assay (ELISA) test. The results of the study showed positive correlation between age, outdoor life style, absence of deworming, absence of flea control measures and levels of allergen-specific IgE. Gender and living area (urban versus rural) did not seem to affect the formation of allergen-specific IgE. According to these findings, evaluating allergen-specific IgE levels, is not a reliable test to diagnose hypersensitivity to food or environmental allergens in cats. On the contrary, this test can be successfully used for diagnosing feline flea bite hypersensitivity.     

Establishment of diagnostic criteria for feline nonflea-induced hypersensitivity dermatitis

Hypersensitivity dermatitides (HD) are commonly seen in cats, and they are usually caused by environmental, food and/or flea allergens. Affected cats normally present with one of the following clinical reaction patterns: head and neck excoriations, usually symmetrical self-induced alopecia, eosinophilic skin lesions or miliary dermatitis. Importantly, none of these clinical presentations is considered to be pathognomonic for HD skin diseases, and the diagnosis of HD is usually based on the exclusion of other pruritic diseases and on a positive response to therapy. The objectives of this study were to propose sets of criteria for the diagnosis of nonflea-induced HD (NFHD). We recruited 501 cats with pruritus and skin lesions and compared clinical parameters between cats with NFHD (encompassing those with nonflea, nonfood HD and those with food HD), flea HD and other pruritic conditions. Using simulated annealing techniques, we established two sets of proposed criteria for the following two different clinical situations: (i) the diagnosis of NFHD in a population of pruritic cats; and (ii) the diagnosis of NFHD after exclusion of cats with flea HD. These criteria sets were associated with good sensitivity and specificity and may be useful for homogeneity of enrolment in clinical trials and to evaluate the probability of diagnosis of NFHD in clinical practice. Finally, these criteria were not useful to differentiate cats with NFHD from those with food HD.     

Serum allergen‐specific immunoglobulin E in atopic and healthy cats: comparison of a rapid screening immunoassay and complete‐panel analysis

Feline and canine atopic dermatitis are thought to have a similar immunopathogenesis. As with dogs, detection of allergen‐specific IgE in cat serum merely supports a diagnosis of feline atopy based on compatible history, clinical signs and elimination of other pruritic dermatoses. In this study, a rapid screening immunoassay (Allercept^® E‐Screen 2nd Generation; Heska AG, Fribourg, Switzerland; ES2G) was compared with a complete‐panel serum allergen‐specific IgE assay (Allercept^®; Heska AG; CP) in healthy cats with no history of skin disease and in atopic cats. The latter had no diagnosis of external parasitism, infection, food hypersensitivity or other skin disease explaining their pruritus, and expressed cutaneous reaction patterns typically associated with feline allergic skin disease (head, neck or pinnal pruritus, miliary dermatitis, self‐induced alopecia, eosinophilic granuloma complex). The proportion of cats positive on either the ES2G or the CP assays was not significantly different between the atopic and healthy cat groups. There was, however, strong agreement between the results of the ES2G and CP assay; overall, the two tests were in agreement for 43 of 49 (88%) serum samples. There was also strong agreement when individual allergen groups were evaluated (agreement noted: indoor, 41 of 49 samples; grasses/weeds, 37 of 49 samples; and trees, 41 of 49 samples). These results indicate that although neither test is diagnostic for feline atopic dermatitis, the screening assay is beneficial for predicting the results of a complete‐panel serum allergen‐specific IgE assay in cats.     

Pilot study: prevalence of positive aeroallergen reactions in 10 cats with small-airway disease without concurrent skin disease

The purpose of this study was to determine the prevalence of positive allergen reactions in cats with small-airway disease (i.e. 'feline asthma', 'feline allergic bronchitis', 'feline bronchial disease'). Intradermal skin tests (IDT) and serum immunoglobulin E (IgE) tests were performed in 10 cats with idiopathic small-airway disease and in 10 normal cats without a history of respiratory disease. None of the cats had a history of skin disease or clinical signs of skin disease at the time of testing. Significantly more individual positive allergen reactions were found on serum IgE tests than on IDT in both groups of cats. Affected cats had significantly more individual positive allergen reactions on both tests than unaffected cats. Both IDT and serum IgE tests resulted in more individual positive allergen reactions to weeds, trees, grasses, and/or moulds in affected cats than in normal cats. Significantly more positive allergen reactions to house dust mites were found in affected compared to non-affected cats by IDT but not by serum IgE testing. One unexpected obstacle to inclusion of more affected cats in the study was the concurrent presence or history of suspect or known allergic skin disease. Concurrent allergic skin disease has not been reported in association with small-airway disease in cats. The increased prevalence of individual positive allergen reactions in affected cats may be due to increased immunological reactivity in these cats. Further studies are needed to answer this question and to determine what role, if any, aeroallergens have in the pathogenesis of this complex feline disease.     

Validation of a novel epicutaneous delivery system for patch testing of house dust mite‐hypersensitive dogs

Background – Patch tests with allergens are used for the evaluation of cellular hypersensitivity to food and environmental allergens in dogs and humans with atopic dermatitis. Viaskin is a novel allergen epicutaneous delivery system that enhances epidermal allergen capture by immune cells. Objectives – To compare the use of Viaskin and Finn chamber patch tests in dogs hypersensitive to mite allergens. Methods – Empty control or Dermatophagoides farinae house dust mite‐containing Viaskin or Finn chamber patches were applied to the thoracic skin of six mite‐hypersensitive Maltese‐beagle crossbred atopic dogs. Lesions were graded 49 and 72 h after patch test application, and skin biopsies were collected after 72 h. Overall microscopic inflammation, eosinophil and T‐lymphocyte infiltrations were scored. Results – Positive macroscopic patch test reactions developed at five of six Viaskin application sites and four of six Finn chamber application sites. Median microscopic epidermal and dermal inflammation, as well as eosinophil and CD3 T‐lymphocyte dermal scores were always higher in biopsies collected at Viaskin than at Finn chamber sites. Microscopic inflammation scores were significantly higher after mite allergen‐containing Viaskin compared with empty patches, but this was not the case for mite‐containing Finn chambers compared with control chambers. Scores obtained using Viaskin were not significantly different from those obtained using Finn chambers. Macroscopic and microscopic scores were significantly correlated. Conclusions and clinical importance – In mite‐allergic dogs, Viaskin epicutaneous delivery systems appear to induce stronger allergen‐specific inflammation than currently used Finn chamber patch tests. Consequently, Viaskin patches might offer a better alternative for screening cellular hypersensitivity to food and environmental allergens.     

犬瘙痒性皮肤病研究进展

瘙痒是犬皮肤病的典型临床症状之一,通常除瘙痒外还常伴脱毛、红斑等皮肤症状。瘙痒问题不仅困扰动物本身,也影响到饲养者的生活质量。瘙痒的发生机制复杂,目前国内外已有大量对人和犬瘙痒性皮肤病的临床和基础研究,揭示了瘙痒和神经免疫系统之间的关系,引入了“瘙痒-抓挠”循环的概念,且表明了免疫系统、皮肤屏障和神经系统的单独促进作用和交互作用是瘙痒产生的关键因素,任一环节的问题都可开启“瘙痒-抓挠”的恶性循环。临床上引起犬瘙痒的病因复杂,参照2007年由国际瘙痒研究论坛成员提出的瘙痒分类,将引起犬瘙痒的疾病根据病因类比对应分为了六大类,引起皮肤病性瘙痒的疾病分为了感染性、过敏性、肿瘤性等,其中在临床上最主要的是犬过敏性瘙痒。犬瘙痒性皮肤病的诊断方法及鉴别诊断多样,需从多方面对患病犬进行信息收集,按一定顺序进行排查和鉴别诊断。犬瘙痒性皮肤病的治疗周期长且疾病易反复,目前常用的西医药物存在副作用大、靶点单一、价格昂贵等不足,中药方剂成分复杂,有效成分多,可从多通路多途径治疗机制复杂的瘙痒,在犬瘙痒性皮肤病的治疗上具有优势和广阔前景。文章对瘙痒发生的机制、犬瘙痒性疾病的分类、诊断及中西医治疗思路等最新研究...     

Food hypersensitivity in 20 dogs with skin and gastrointestinal signs

Canine food allergy can be defined as a non-seasonal, pruritic skin disorder of dogs that is associated with the ingestion of a substance found in the dog's diet. This study records the use of a proprietary dried fish, corn and soyabased diet for the investigation and maintenance of food allergic dogs when fed initially as a restricted allergen diet and then as a maintenance diet after challenge. All the dogs showed evidence of pruritic skin disease and in addition demonstrated gastrointestinal signs. These included the presence of faecal mucus and blood, tenesmus and increased faecal frequency; all the signs associated with colitis. Both cutaneous and gastrointestinal signs resolved when an elimination diet was fed and could be reproduced when the animal was appropriately challenged. Ten dogs were trailed on a home cooked diet of fish and potato and 10 dogs on the proprietary complete food. All the dogs were challenged to identify their food allergies. Nineteen of the dogs have subsequently been successfully maintained on the proprietary food.     

Response to intradermal skin testing with four cat allergen preparations in healthy and allergic dogs

Intradermal skin testing with 4 cat allergens was performed on 40 dogs. The allergens used were a commercial preparation, cat allergen 1, cat pelt extract, and cat serum. Twenty dogs had inhalant allergies (canine atopy) and 20 dogs were healthy. The dogs in these 2 groups were further allotted to groups of dogs with or without exposure to cats. Cat pelt extract was the only allergen that caused a statistically significant (P less than 0.025) difference in the number of positive reactions in healthy vs allergic dogs, with healthy dogs having the greater number of positive reactions. Seven (35%) of the 20 dogs with no known exposure to cats had positive reactions to at least one of the allergens. In dogs that had been exposed to cats, positive reactions developed in twice the number of dogs without clinical signs of canine atopy, compared with those with clinical signs of canine atopy. These data showed that dogs do become sensitized to cat allergen, but that this sensitization may not indicate known exposure to cats or clinical disease.     

Intradermal skin tests in equine dermatology: a study of 83 horses

Allergic diseases are often diagnosed clinically in the horse without performing diagnostic tests. The purpose of this work was to contribute to the validation of intradermal skin tests in the horse. Eighty-three horses, 14 showing skin or respiratory signs of supposed allergic origin, were subjected to an intradermal skin test using 6 different allergens, positive and negative controls. The tests were read for all animals after 20 min, and for 29 horses after 1 and 4 h. Additionally, 19 horses were tested a few months apart. The comparison after 20 min of the cutaneous reactions to allergens and to positive and negative controls allowed us to propose a threshold of positivity; skin reactions with a diameter above or equal to 15 mm, or with at least a 13 mm diameter and a skin thickness similar to the positive control. There was a marked difference between the healthy group and the allergic group for Culex pipiens and Dermatophagoides farinae, although positive reactions were not rare in the healthy group. Tabanus sp. gave positive reactions in both healthy and allergic animals. There was no significant variation in the reactions observed after 20 min and after 60 min. After 4 h, the progression of the reactions was highly variable and negative controls showed a certain number of positive reactions, which negated their reliability at the point in time, and made it difficult to interpret the other allergens. Finally, the repeatability of intradermal skin tests reactions after 20 min was poor, and probably related to the influence of seasonality for some of the allergens. Further studies are required, notably with others allergens, to interpret intradermal skin tests' responses in clinical practice.     

P-58 Three cases of pathological dermal deposits associated with internal diseases in dogs (xanthomatosis, calcinosis and amyloidosis)

Intestinal parasites have been anecdotally associated with pruritus in dogs. A relationship was proposed when the elimination of a specific parasite resolved the pruritus, and re-infection with a parasite caused the pruritus to recur. Ascarids, coccidia, hookworms, tapeworms and whipworms have all been incriminated. Recent reports in the human and veterinary literature have suggested that there may be a relationship between Giardia infection and the development of pruritus and other allergic signs. In order to determine if there is an association between infection with Giardia and pruritus in dogs, faecal samples were collected from 71 pruritic dogs and 101 clinically normal dogs. Three faecal samples from each animal were analysed using a zinc-sulphate concentration technique for the presence of Giardia cysts, and one randomly selected faecal sample from each dog was analysed with an ELISA for Giardia -specific antigen. Ten of 101 dogs (9.9%) in the clinically normal group tested positive with the ELISA, and Giardia cysts were detected in the faeces of seven of these antigen-positive dogs. No Giardia cysts were found in the dogs that tested negative with the ELISA. None of the dogs in the pruritic group tested positive for Giardia by either method. The results indicated a negative association between Giardia infection and pruritic skin disease ( P  = 0.006). Cephalexin was commonly used in the pruritic group, but not in the control group, and may therefore be an explanatory variable.
Funding: Ontario Veterinary College Pet Trust.     

Correlation of histologic and immunologic findings in cats with miliary dermatitis

Eighteen cats with miliary dermatitis were evaluated, using skin testing and histology. Sixteen cats had allergic skin disease (14 cats had positive skin-test reactions to flea antigen [two of which were also atopic], one was atopic only, and one was allergic to beef). In the two remaining cats, the cause of miliary dermatitis was not identified. Histologically, 17 of the cats had superficial eosinophilic dermatitis and epidermal spongiosis, crusting, and ulceration, which were compatible with an allergic cause. Four of these cats had concurrent eosinophilic plaques, which histologically resembled miliary lesions. This overlap of plaques with miliary lesions indicated that when plaques and miliary dermatitis are found concurrently, both lesions may be caused by the same allergens.     

Interleukin 31 and targeted vaccination in a case series of six horses with chronic pruritus

Chronic pruritus is defined as prolonged itching symptoms associated with a variety of skin conditions. These pruritic conditions clinically manifest in a dermatitis phenotype and commonly are of allergic origin with hypersensitivities towards environmental allergens. Interleukin-31 (IL-31) is a common player in allergic pruritus across species. The objective of the study was evaluation of the clinical efficacy of a therapeutic vaccine targeting IL-31 in horses with chronic pruritus of unknown origin (CPUO) and that could not be explained by insect bite hypersensitivity (IBH). This consecutive case series pilot study included client-owned horses with a long history of CPUO. Four horses affected by year-round CPUO were vaccinated with a vaccine consisting of equine IL-31 (eIL-31) covalently coupled to a virus-like particle (VLP) derived from cucumber mosaic virus containing a tetanus toxoid universal T cell epitope (CuMV_TT). Clinical signs and pruritic behaviour were documented by photography and owner questionnaire pre and post vaccination. In addition, in three CPUO horses, levels of IL-31, thymic stromal lymphopoietin (TSLP) and monocyte chemoattractant protein 1 (MCP-1) were quantified from skin punch biopsies. IL-31, TSLP and MCP-1 levels were upregulated in pruritic, alopecic skin lesions compared to healthy skin of the same horse. Clinical signs and pruritic behaviour improved in all four horses upon vaccination with eIL-31-CuMV_TT vaccine. The vaccine was well tolerated without safety concerns throughout the study. The main limitations of this study are the absence control treated horses and allergy diagnostics. It was concluded that Anti-IL-31 therapy might be applied as an allergen-independent treatment option for horses with CPUO overcoming the challenges of identifying the allergic trigger.     

Straelensiosis in two cats and ten dogs from Israel

Straelensiosis is uncommonly described outside Europe. This report describes straelensiosis in two cats and in ten dogs diagnosed with the disease outside Europe. Both cats displayed erythematous macules or nodules on the abdominal skin. One cat was extremely pruritic, while in the other the lesions were incidental findings when the cat was presented for neutering. The mites were noted in skin scrapings in both cats and histopathologically in one cat. All dogs showed a general distribution of papules, and intense pruritus was noted in six dogs. The diagnosis in all dogs was based on histopathology. Treatment of the animals in this study varied, and among the various administrated treatments, amitraz showed promising results.     

Diagnostic testing of dogs for food hypersensitivity

Thirteen food-allergic dogs were studied to evaluate the efficacy of feeding a commercially available egg and rice diet, intradermal skin testing, and serologic testing by ELISA for diagnosing and/or characterizing food hypersensitivity. Feeding of a home-cooked whole lamb meat and rice diet for 3 weeks, followed by challenge with each dog's regular diet, served as the standard for diagnosing food hypersensitivity. Each dog underwent provocative testing with 6 individual ingredients to determine as many of its dietary allergens as possible. Prior to skin testing and serologic testing by ELISA, most dogs had been recently exposed to the offending diet and subsequently manifested clinical signs of allergy. All dogs that tolerated the aforementioned commercial diet were exposed to it for at least 7 weeks; 84.6% of food-hypersensitive dogs ate the commercial diet with impunity. Of the 2 reactors to the commercial diet, only 1 became pruritic in response to provocation testing with chicken eggs. Low sensitivity and high specificity were found for skin testing and the ELISA, indicating a lack of true- and false-positive reactions. Neither the positive nor negative predictive values adequately predicted positive and negative reactions, respectively, for either test. On the basis of these results, the commercial diet, skin testing, and anti-IgE ELISA cannot replace an owner-prepared food elimination diet for food hypersensitivity testing in dogs.     

Preliminary investigations into the use of allergy skin testing solutions and desensitizing vaccines in dogs

Dogs suffering from chronic pruritus of unknown aetiology are a persistent problem for small animal practitioners. Many cases are classified as ‘allergic’ or ‘atopic’ even though little work has been carried out on the incidence or diagnosis of these conditions in Britain. Skin testing has been attempted but few published reports are available. Practitioners were supplied with skin testing kits containing a range of allergens to which dogs may be exposed and were asked to test clinical cases of pruritus which they considered might be of allergic aetiology. Positive reactions were obtained most commonly to house dust and house dust mite (Dermatophagoides pteronyssinus) antigens. In several cases the skin test results correlated with the symptoms and case history. Results suggest that in certain cases skin testing may be beneficial in diagnosis, although further immunological experimental work is necessary to evaluate more fully the technique. Desensitization therapy was attempted in several cases with fairly successful clinical results.     

Evaluation of risk factors for Cryptococcus gattii infection in dogs and cats

OBJECTIVE: To determine risk factors associated with Cryptococcus gattii infection in dogs and cats residing on Vancouver Island in British Columbia, Canada. DESIGN: Matched case-control study. ANIMALS: 20 dogs and 29 cats with C gattii infection and matched controls. PROCEDURE: Dogs and cats with a confirmed or probable diagnosis of cryptococcosis resulting from infection with C gattii were enrolled by veterinarians, and owners completed a questionnaire designed to obtain information pertaining to potential risk factors for the disease. Owners of matched control animals were also interviewed. Odds ratios and 95% confidence intervals or paired t tests were calculated to determine significant associations. RESULTS: Animals were enrolled during 2 noncontiguous periods in August 2001 to February 2002 (8 dogs and 9 cats enrolled) and May to December 2003 (12 dogs and 20 cats enrolled). Risk factors significantly associated with development of cryptococcosis included residing within 10 km of a logging site or other area of commercial soil disturbance, above-average level of activity of the animal, travelling of the animal on Vancouver Island, hunting by the animal, and owners hiking or visiting a botanic garden. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that dogs and cats that were active or that lived near a site of commercial environmental disturbance had a significantly increased risk of developing C gattii infection. Veterinarians should communicate these risks to owners in context because cryptococcosis was an uncommon disease in this population.     

Diagnosis and management of food allergy and intolerance in dogs and cats

SUMMARY This paper reviews food allergy and intolerance in dogs and cats. Adverse reactions to ingested food components can affect many systems and can produce signs involving the skin, gastrointestinal tract, respiratory tract and central nervous system, and these clinical signs are reviewed. Most basic food ingredients have the potential to induce an allergic response, although most reactions are caused by proteins. In particular, dogs and cats can become sensitive to cow's milk, beef, fish or cereal. Food allergy and intolerance is rare in dogs and cats, although the incidence in practice is difficult to establish. Clinical signs are quite variable, depending on the individual response, although the major clinical sign is pruritus. Diagnosis can be difficult, as there is no single test available to help the clinician to confirm or refute the presence of food sensitivity. Diagnosis is based on dietary investigation in the form of elimination diets and test meals. Elimination diets for dogs include lamb, chicken, rabbit, horse meat and fish as sources of protein, with rice or potatoes. Successful elimination diets for cats include lamb, chicken, rabbit or venison, with rice. Improvement in clinical signs while on the elimination diet is suggestive of food allergy. The diagnosis should be confirmed by feeding the original diet, with the development of clinical signs within 7 to 14 days of feeding.     

Treatment of canine atopic dermatitis: 2010 clinical practice guidelines from the International Task Force on Canine Atopic Dermatitis

Atopic dermatitis (AD) is a common chronic relapsing pruritic skin disease of dogs for which treatment has varied over time and geographical location. Recent high quality randomized controlled trials and systematic reviews have established which drugs are likely to offer consistent benefit. The International Task Force for Canine AD currently recommends a multi‐faceted approach to treat dogs with AD. Acute flares should be treated with a combination of nonirritating baths and topical glucocorticoids, once an attempt has been made to identify and remove the suspected causes of the flare. Oral glucocorticoids and antimicrobial therapy must be added when needed. In dogs with chronic AD, a combination of interventions should be considered. Again, factors that trigger flares of AD must be identified and, if possible, avoided. Currently recognized flare factors include food, flea and environmental allergens, Staphylococcus bacteria and Malassezia yeast. Skin and coat hygiene and care must be improved by bathing with nonirritating shampoos and dietary supplementation with essential fatty acids. The severity of pruritus and skin lesions can be reduced with a combination of anti‐inflammatory drugs. Currently, medications with good evidence of high efficacy include topical and oral glucocorticoids, and calcineurin inhibitors such as oral ciclosporin and topical tacrolimus. The dose and frequency of administration of these drugs should be tailored to each patient considering each drug’s efficacy, adverse effects and cost. Allergen‐specific immunotherapy should be offered, whenever feasible, in an attempt to prevent recurrence of clinical signs upon further exposure to environmental allergens to which the patient is hypersensitive.     

Multiple-center study of reduced-concentration triamcinolone topical solution for the treatment of dogs with known or suspected allergic pruritus

OBJECTIVE: To determine the efficacy of triamcinolone acetonide topical solution (TTS) in dogs for use in reduction of clinical signs of pruritic inflammatory skin diseases of a known or suspected allergic basis and to evaluate adverse effects associated with TTS administration. ANIMALS: 103 pruritic adult dogs with known or suspected allergic skin disease. PROCEDURE: Dogs were treated for 4 weeks with TTS or with vehicle solution (control dogs) in a multiple-center study. Clinical signs were scored by owners and by examining veterinarians before and after treatment. Blood samples obtained before and after treatment were subjected to routine hematologic and serum biochemical analyses. RESULTS: Treatment success, as defined by an improvement of at least 2 of 6 grades in overall clinical score, was evident in 35 of 52 (67%) TTS-treated dogs (mean improvement, 1.98) and 12 of 51 (24%) control dogs (mean improvement, 0.29). For several criteria, TTS was significantly more effective than vehicle in reducing clinical signs. Minor alterations in hematologic determinations in TTS-treated dogs were limited to slightly lower total leukocyte, lymphocyte, and eosinophil counts after treatment. Minor adverse effects were reported by owners in 6 of 52 (12%) TTS-treated and 9 of 51 (18%) control dogs. CONCLUSIONS AND CLINICAL RELEVANCE: Triamcinolone used as a spray solution at a concentration approximately one-sixth the concentration of triamcinolone topical preparations currently available for veterinary use is effective for short-term alleviation of allergic pruritus in dogs. Adverse effects are few and mild and, thus, do not preclude prolonged treatment with the solution.