猫特应性皮炎综合征的治疗-系统性回顾（2）

王帆

Treatment of the feline atopic syndrome – a systematic review

猫特应性皮炎综合征的治疗-系统性回顾

作者：Ralf S. Mueller* , Tim Nuttall† , Christine Prost‡, Bianka Schulz* and Petra Bizikova§

翻译：王帆

Systemic glucocorticoids

全身性糖皮质激素

Analysis of evidence

证据分析

Three prospective double-blinded RCTs evaluated systemic glucocorticoid treatment in cats with FASS. One prospective study looked at the diabetogenic potential of prednisolone and dexamethasone in healthy cats. The three clinical trials included 63 cats: 11 treated with prednisolone, 36 with methylprednisolone and 16 with triamcinolone. The treatment regimens used dosages of 1 mg/kg once daily of prednisolone, 0.77 mg/kg twice daily (20 cats) to 1.4 mg/kg once daily (16 cats) of methylprednisolone, and 0.18 mg/kg once daily of triamcinolone acetonide for 28 to 84 days. The latter study used daily treatment for ≤14 days to achieve remission and then tapered treatment resulting in final alternate day dosages of 0.54 mg/kg methylprednisolone and 0.08 mg/ kg triamcinolone.Pruritus was assessed using a 0–10 Visual Analog Scale (pVAS) in two studies and a 0– 5 Linear Analog Scale in one. Lesion scores were assessed using the Canine Atopic Dermatitis Extent and Severity Index, 2nd iteration (CADESI-02), a Feline Erythema, Excoriation and Alopecia score (FEEAS; a modified CADESI-03 score omitting lichenification), and a Scoring Feline Allergic Dermatitis (SCORFAD) scale. Only the SCORFAD scale had been validated for pruritic and eosinophilic skin lesions in cats. One study included a validated Quality of Life (QoL) score. The cats presented with pruritus and a variety of the recognised reaction patterns associated with FASS. Most cats presented with more than one type of lesion. The seasonality of the clinical signs was not recorded.

三项前瞻性双盲随机对照试验评估了FASS患猫的全身性糖皮质激素治疗。一项前瞻性研究观察了泼尼松龙和地塞米松会导致健康猫患糖尿病的潜在可能。三个包括63只猫的临床试验:11只使用泼尼松龙，36只使用甲基泼尼松龙，16只使用曲安奈德。治疗方案使用剂量为1mg/kg每日一次的泼尼松龙，0.77mg/kg每日两次(20只猫)至1.4mg/kg每日一次(16只猫)的甲基泼尼松龙，0.18mg/kg每日一次的曲安奈德，持续28至84天。后一项研究使用每日一次治疗≤14天达到缓解，然后逐渐减少治疗剂量，最终使用剂量为0.54mg/kg的甲基泼尼松龙和0.08mg/kg的曲安奈德。两项研究用0-10视觉模拟量表(pVAS)评估瘙痒，一项研究用0-5线性模拟量表评估瘙痒。采用第二代犬特应性皮炎严重程度指数(CADESI-02)进行病变评分，猫红斑、抓痕和脱毛评分(FEEAS;一种改良CADESI-03评分(不含苔藓化)和猫过敏性皮炎评分(SCORFAD)量表。只有SCORFAD量表被证实可用于猫的瘙痒性和嗜酸性皮肤病变。其中一项研究包括验已验证的生活质量(QoL)评分。这些猫表现出瘙痒和与FASS相关的各种已知的反应模式。大多数猫都有不止一种类型的病变。临床症状的季节性没有记录。

One cross-over RCT compared oral prednisolone at 10 mg/day with inhaled flunisolide at 250 μg twice daily in six cats with feline asthma experimentally sensitised to Bermuda grass. Another cross-over RCT treated six cats sensitised to A. suum with either oral prednisolone at 1 mg/kg twice daily, 500 mcg of inhaled fluticasone proprionate twice daily, or a combination of inhaled fluticasone propionate and salbutamol at 500 mcg and 50 mcg, respectively, for four consecutive days. A study with 14 client-owned cats with lower airway disease assessed airway function before and after prednisolone therapy.

一项交叉随机对照试验比较了6只对百慕大草过敏患猫，口服10mg /天的泼尼松龙与吸入250μg/次，每天两次的氟尼缩松。另一项交叉随机对照试验治疗6只对猪蛔虫过敏患猫，即口服泼尼松龙1mg/kg，每日2次，有吸入丙酸氟替卡松500mcg，每日2次，或者同时吸入500mcg丙酸氟替卡松和50 mcg沙丁胺醇，连用4天。一项对14只患下呼吸道疾病的家养猫的研究评估了泼尼松龙治疗前后的气道功能。

Analysis of efficacy

疗效评估

Treatment outcome data were available for 63 cases with FASS (see Table 4). Cats that responded to treatment were reported to do so within 7–14 days. There was no association between the responses to treatment and the type of lesions.

63例FASS病例的治疗结果数据(见表4)。据报道，对治疗有效的患猫在7 - 14天内就有治疗效果。治疗效果与病变类型之间没有关联。

Although prednisolone decreased allergen-specific IgE and the percentage of eosinophils in the BALF of cats experimentally sensitised to Bermuda grass, it did not improve airway hyper-reactivity in response to methacholine.In the A. suum-sensitised cats there were no significant differences in respiratory rate or Penh [an estimate of airflow limitation measured by conventional barometric whole body plethysmography (BWBP)]between the treatment groups.Allergen-induced airway hyperresponsiveness was significantly inhibited by the oral prednisolone, inhaled fluticasone proprionate and inhaled fluticasone propionate/salbutamol. The mean BALF eosinophil percentage was lower after oral and inhaled corticosteroid treatment and these changes were significant for groups receiving prednisolone and the combination of inhaled fluticasone propionate/salbutamol, although the dose of inhaled fluticasone was fairly high. In the study with client-owned cats with lower airway disease, a significantly decreased peak to mid-expiratory flow and no significant changes in other BWBP parameters were noted after at least three weeks of therapy with prednisolone at 1.2–2 mg/kg once daily.

虽然泼尼松龙降低了实验诱导对百慕大草过敏患猫BALF中过敏原特异性IgE和嗜酸性细胞的比例，但它并没有改善对甲基胆碱反应的气道超反应性。在对猪蛔虫过敏患猫中，试验组之间在呼吸频率或Penh(一种用常规气压式全身体积描图(BWBP)测量的气流限制估计值)方面没有显著差异。口服泼尼松龙、吸入丙酸氟替卡松和吸入丙酸氟替卡松/沙丁胺醇显著抑制过敏原诱导的气道高反应性。口服和吸入皮质类固醇治疗后，BALF嗜酸性细胞平均比例较低，这些变化在接受泼尼松龙和吸入丙酸氟替卡松/沙丁胺醇联合治疗组中疗虚显著，但是吸入氟替卡松的剂量相当高。在对患有下呼吸道疾病的家养猫的研究中，在使用1.2 -2 mg/kg每日一次的泼尼松龙治疗至少三周后，发现其呼气峰至呼气中期流量显著下降，其他BWBP参数无显著变化。

Adverse effects

副作用

Clinical adverse effects were uncommon, with one case each of vomiting and lethargy among the 20 cats treated with methylprednisolone.Clinicopathological abnormalities included increased liver enzymes in one of 16 triamcinolone- and eight of 36 methylprednisolone-treated cats. Hyperglycaemia was seen in four, altered haematological parameters in four, and glycosuria in one of the 36 methylprednisolone-treated cats. Mean albumin and fructosamine levels significantly increased in triamcinolone-(n=16) and methylprednisolone-treated cats (n=16) and remained within the reference ranges. Amylase was elevated above the reference range in 10 of 15 triamcinolone- and two of 14 methylprednisolone-treated cats at the end of the induction phase, and returned to normal during the every other day maintenance phase. The safety study evaluated 14 cats treated with either 4.4 mg/kg once daily of prednisolone or 0.55 mg/ kg once daily of dexamethasone for 56 days. Dexamethasone treatment resulted in significantly increased fructosamine concentration, decreased insulin sensitivity and secretion, and increased glycosuria, although the cats did not become hyperglycaemic at any point. No adverse effects were mentioned in most of the studies evaluating asthmatic cats.One study evaluated long-term effects of glucocorticoids in asthmatic cats and found adverse effects such as polyuria and polydipsia, diabetes mellitus and fungal infection in four of 34 cats. A study evaluating long-term safety (at least three years) of methylprednisolone in 25 cats detected an increase of triglycerides, amylase and monocytes, yet changes remained within the reference interval.

临床副反应不常见，在20只甲泼尼龙治疗组患猫中，呕吐和嗜睡病例各有一例。临床病理异常包括16只曲安奈德治疗组中的1只患猫和36只甲基泼尼松龙治疗组中的8只患猫肝酶升高。在36只甲基泼尼松龙治疗组中，有4只患猫出现高血糖症，4只患猫出现血液学参数改变，1只患猫出现尿糖。在曲安奈德治疗组(16只)和甲基泼尼松龙治疗组(16只)患猫平均白蛋白和果糖胺水平显著升高，并保持在参考范围内。15只曲安奈德治疗组中10只患猫，14只甲基泼尼松龙治疗组中2只患猫，在诱导期结束时淀糖酶升高到参考范围以上，在隔日一次的维持期时恢复正常。安全性研究评估了14只患猫，它们分别接受4.4mg/kg每日一次的泼尼松龙或0.55mg/kg每日一次的地塞米松治疗56天。地塞米松治疗组果糖胺浓度显著增加，胰岛素敏感性和分泌量降低，并尿糖升高，但患猫在任何时候都没有出现高血糖。在大多数评估哮喘患猫的研究中没有提到副作用。一项研究评估了糖皮质激素对哮喘患猫的长期影响，发现34只患猫中有4只出现了副反应，如多饮多尿、糖尿病和真菌感染。一项在25只患猫中评估甲基泼尼松龙长期安全性(至少3年)的研究发现，甘油三酯、淀粉酶和单核细胞增加，但变化仍在参考区间内。

Recommendations

建议

Systemic glucocorticoids are rapid and effective in most cats with FASS (QOE 1; SOR A). Treatment with 1.4– 1.5 mg/kg once daily of methylprednisolone-induced remission in 33 of 36 cats within 14 days. The similar response to 0.18 mg/kg once daily of triamcinolone acetonide suggests that this drug has seven-fold greater potency than methylprednisolone. It is therefore likely that equipotent doses of other glucocorticoids will be likewise effective (QOE 3; SOR C). By contrast, 1 mg/kg once daily of prednisolone (approximately 50% of the above dosages) was much less effective. Once in remission, treatment can be tapered to the lowest and least frequent dosage that maintains remission (QOE 1; SOR A). On average, this equated to 20–25% of the starting dosage. Once-daily treatment is advised (QOE 1; SOR A). There was no difference in the efficacy of methylprednisolone at 0.77 mg/kg twice daily and 1.4 mg/kg once daily. One study noted that twice-daily dosing reduced QoL scores.Systemic glucocorticoids at these doses were well-tolerated, although all of the studies were short-term. However, altered haematology, serum biochemistry and urinalysis parameters were frequent (particularly markers of glucose metabolism). Regular monitoring of cats on a long-term treatment with systemic glucocorticoids is therefore warranted, especially with more diabetogenic drugs such as dexamethasone (QOE 1, SOR A).

全身糖皮质激素对大多数FASS患猫快速且有效(QOE 1; SOR A)。对36只患猫使用1.4-1.5mg/kg每日一次的甲基泼尼松龙连用14天治疗，33只缓解。与每日一次0.18mg/kg的曲安奈德治疗疗效相似，表明该药的效价是甲泼尼龙的7倍。因此，等效剂量的其他糖皮质激素可能也同样有效(QOE 3; SOR C)。相比之下，1 mg/kg每天一次的泼尼松龙(约为上述剂量的50%)的效果要差得多。一旦缓解，治疗可以逐渐减少到维持缓解的最低频率剂量(QOE 1;SOR A)。平均而言，这相当于开始剂量的20-25%。建议每日一次治疗(QOE 1; SOR A)。甲泼尼龙0.77 mg/kg每日两次和1.4 mg/kg每日一次的疗效没有差异。一项研究指出，每天两次给药会降低生活质量评分。虽然这些剂量的全身糖皮质激素耐受性良好，但是所有的研究都是短期的。然而，常发生血液学、血清生化和尿分析参数改变(特别是葡萄糖代谢标记)。因此，有必要对长期服用糖皮质激素的猫进行定期监测，特别是使用会更多导致糖尿病的药物，如地塞米松(QOE 1, SOR A)。

In feline asthma, there is good evidence for clinical efficacy of oral glucocorticoids (QOE 1; SOR A) although most of this evidence is based on experimentally sensitised cats.

对于猫哮喘，虽然证据表明口服糖皮质激素临床效果良好(QOE 1; SOR A)，但大多数证据都是基于实验室诱导敏感患猫。

Topical and inhaled glucocorticoids

外用和吸入式糖皮质激素

Analysis of evidence

证据分析

There was one prospective open and uncontrolled clinical trial of topical 0.0584% hydrocortisone aceponate (HCA, Cortavance, Virbac; Carros, France) in 10 cats with perennial pruritus and lesions consistent with FASS. The cats were treated with two sprays per 10 x 10 cm area of affected skin from 10 cm away daily for 28 days, followed by every other day dosing up to Day (D). The outcome measures included a pVAS, a validated Feline Dermatitis Extent and Severity Index lesion score (FeDESI), and a five point categorical score for efficacy, tolerance and ease-of-administration.

有一项前瞻性开放和不受控制的临床试验，10只常年瘙痒且病变与FASS一致的患猫外部使用0.0584%氢化可的松醋丙酯(HCA）。患猫病变皮肤每10 x 10厘米面积距离皮肤10厘米远，连喷2下，每日一次，连用28天,随后隔日一次给药。治疗结果监测包括pVAS、已验证的猫皮肤病变严重程度指数评分(FeDESI)和一个5分制疗效评分、耐受性和易于管理性。

Four studies evaluated the use of inhaled glucocorticoids in an experimental model of feline asthma. In one study, inhaled flunisolide at 250 μg twice daily was compared with oral prednisolone at 10 mg once daily in six cats. In the second blinded cross-over RCT the effect of three different dosages of inhaled fluticasone propionate delivered by a metered-dose inhaler was investigated in six cats with experimentally induced allergic airway inflammation. A third cross-over RCT treated six cats sensitised to A. suum with either prednisolone (1 mg/kg twice daily), inhaled fluticasone propionate (500 mcg twice daily), or a combination of inhaled fluticasone propionate and salbutamol (500 mcg/50 mcg twice daily) for four consecutive days. In another study, sensitised cats underwent RIT and for the first six months concurrently received either oral prednisolone at 10 mg/ kg/day/cat or 220 mcg twice-daily inhaled fluticasone/ cat. One study investigated the effects of 400 mcg of inhaled budesonide twice daily on 37 cats with naturally occurring asthma and chronic bronchitis in a retrospective study using client questionnaires.

四项研究评估了吸入糖皮质激素在猫哮喘实验模型中的使用。在一项研究中，6只猫每天两次吸入250μg氟尼缩松，与每天一次口服10mg泼尼松龙进行比较。在第二个盲性交叉随机对照试验中，研究了用计量吸入器吸入三种不同剂量丙酸氟替卡松对6只实验性致敏呼吸道炎症患猫的影响。第三个交叉随机对照试验用泼尼松龙(1mg/kg，每日2次)、吸入丙酸氟替卡松(500mcg，每日2次)或吸入丙酸氟替卡松联合沙丁胺醇(500mcg/50mcg，每日2次)，连续4天治疗对猪蛔虫过敏的6只猫。在另一项研究中，过敏患猫接受了RIT治疗，并在前六个月每只猫每天同时接受10mg/kg的口服泼尼松龙或每只猫每天两次吸入220mcg氟替卡松。一项回顾性研究通过客户问卷调查，调查了每天两次吸入400mcg布地奈德，对37只患有哮喘和慢性支气管炎的猫的影响。

Analysis of efficacy

疗效分析

Three cats were withdrawn from the HCA study; two were lost to follow-up and one was removed owing to poor efficacy.Using an intention-to-treat analysis, there was a 77% reduction in FeDESI score and 76% reduction in pruritus by D56. Over 50% of the improvement was seen by D14. Ease-of-administration, tolerance and efficacy assessments were good-to-excellent in the seven cats that completed the study. Of these cats, six of seven could be maintained on every other day treatment and one required daily therapy.

3只猫退出了HCA研究，2例失访，1例因疗效不佳而中断。使用意向治疗分析，到第56天时，FeDESI评分下降77%，瘙痒下降76%。超过50%病例第14天有改善。在完成研究的7只猫中，易于管理、耐受性和有效性评估都是良好到优秀。在这些猫中，7只中的6只可以维持隔日一次治疗，1只需要每天治疗。

Although inhaled flunisolide decreased allergen-specific IgE and the number of eosinophils in the BALF of cats experimentally sensitised to Bermuda grass (Table 5), it did not improve airway hyper-reactivity to methacholine. Fluticasone dosages of 44, 110 or 220 mcg twice daily for three weeks did not suppress the hypothalamic–pituitary–adrenal axis. In the same experimental model, inhaled fluticasone did not influence the outcome of RIT in contrast to oral glucocorticoids (where airway eosinophilia was significantly increased after nine months of RIT), although the dose of prednisolone was very high. In the study with the six cats sensitised to A. suum, inhaled fluticasone propionate, or a fluticasone propionate and salbutamol combination, resulted in significantly decreased allergen-induced airway hyper-responsiveness. The mean BALF eosinophil percentage was significantly lower after the inhaled combination of fluticasone and salbutamol. In the study of naturally occurring asthma or chronic bronchitis treated with budesonide, close to a third of the cats were asymptomatic with therapy, almost as many improved (Table 5). BWBP parameters had improved in the 19 cats where pre- and postexaminations were available.

虽然吸入氟尼缩松降低了对百慕大草实验室致敏患猫BALF中的过敏原特异性IgE和嗜酸性细胞数量(表5)，但它并没有改善气道对甲胆碱的高反应性。氟替卡松剂量为44、110或220mcg，每日2次，连续3周，并没有抑制下丘脑-垂体-肾上腺轴。在相同的实验模型中，吸入氟替卡松与口服糖皮质激素相比没有影响RIT的结果(RIT后9个月气道嗜酸性细胞显著增加)，但是泼尼松龙的剂量非常高。在对6只对猪蛔虫过敏患猫进行的研究中，吸入丙酸氟替卡松，或丙酸氟替卡松和沙丁胺醇的组合，使过敏原引起的气道高反应性显著降低。吸入氟替卡松和沙丁胺醇后，BALF平均嗜酸性细胞比例显著降低。在布地奈德治疗自然发生的哮喘或慢性支气管炎的研究中，接近三分之一的患猫在治疗后无症状，几乎同样多的猫得到了改善(表5)。19只猫治疗前和治疗后检查的BWBP参数得到了改善。

Adverse effects

副作用

In the study using HCA in cats with FASS, no adverse events were noted and there were no haematological, biochemical or urine abnormalities in samples from four of the cats. Four cats would not tolerate the spray and the solution was applied directly using cotton wool. There was no association between the response to treatment and lesion type. In studies evaluating feline asthma, clinical adverse effects to inhaled glucocorticoids were either not seen or not mentioned.Inhaled budesonide therapy was associated with hypothalamic–pituitary–adrenal axis suppression in one study.

在对FASS患猫使用HCA的研究中，没有注意到副反应，4只猫没有发现血液、生化或尿液异常。有4只猫无法耐受喷雾形式，于是用棉花直接沾溶液擦拭。治疗效果与病变类型之间没有关联。在评估猫哮喘的研究中，吸入糖皮质激素的临床副作用要么没有看到，要么没有提到。在一项研究中，吸入布地奈德治疗与下丘脑-垂体-肾上腺轴抑制有关。

Recommendations

建议

Topical 0.0584% HCA was rapidly effective in seven of 10 cats (QOE2; SOR B). It is likely that other topical glucocorticoids also will be effective depending on the type and formulation of glucocorticoid (QOE 3; SOR C) and topical treatment should be considered for FASS whenever feasible (QOE 3; SOR C). This is likely to have fewer adverse effects than systemic glucocorticoid treatment. However, these products are not licenced for cats, systemic absorption is possible and regular clinical monitoring is advised. There is good evidence that inhaled glucocorticoids are beneficial for cats with asthma (QOE 1; SOR A). No clinical adverse effects were reported, although again monitoring of cats on long-term treatment is advised. Hypothalamic–pituitary–adrenal axis suppression was documented with high doses of inhaled flunisolide and budesonide.

外用0.0584% HCA对10只猫中的7只快速且有效(QOE2; SOR B)。其他外用糖皮质激素也可能有效，这取决于糖皮质激素的类型和配方(QOE 3; SOR C),如果可行，应考虑外部治疗FASS(QOE 3; SOR C)。这可能比全身性糖皮质激素治疗有更少的副作用。但是，这些产品不允许用于猫，可能会全身吸收，并建议定期临床监测。有充分的证据表明吸入糖皮质激素对哮喘患猫有效(QOE 1; SOR A)。没有临床副反应的报告，但长期治疗建议再次对患猫进行监测。在吸入高剂量氟尼缩松和布地奈德时，下丘脑-垂体-肾上腺轴受到抑制。

Ciclosporin

环孢素

Analysis of evidence

证据分析

Ciclosporin use in FASS was evaluated in two doubleblinded, placebo-controlled studies, one doubleblinded, prednisolone-controlled study, three prospective open studies, one safety and tolerability study,and three retrospective case series. In two studies, specific clinical presentations were not mentioned, while the other studies included cats with excoriations as a consequence of pruritus ( 185), self-induced alopecia (n=181), eosinophilic granuloma (n=112) and miliary dermatitis (n=100). Most cats presented with more than one lesion type. There is one case report of a cat with asthma, congestive heart failure and diabetes mellitus treated successfully with ciclosporin. Two other studies evaluated the effect of ciclosporin on mast cell degranulation and airway remodelling in a colony of cats sensitised to A. suum. In older studies, a human product of ciclosporin was used (Neoral, Novartis; Basel, Switzerland), whereas in newer studies, the veterinary product was administered (Atopica, Novartis) and in one study both products were used.

两项双盲、安慰剂对照研究、一项双盲、泼尼松龙对照研究、三项前瞻性开放研究、一项安全性和耐受性研究和三项回顾性病例分析研究评估了环孢素在FASS中的应用。在两项研究中，没有提到具体临床表现，但其他研究包括瘙痒导致的抓痕(185只)、自发性脱毛(181只)、嗜酸性肉芽肿(112只)和粟粒性皮炎(100只)。大多数猫都有一种以上的病变类型。有一个病例报告一只同时患猫哮喘、充血性心力衰竭和糖尿病使用环孢素成功治疗。另外两项研究评估了环孢素对猪蛔虫过敏患猫的肥大细胞脱颗粒和气道重塑的影响。在更早的研究中，使用了人用药环孢素(Neoral, Novartis; Basel, Switzerland)，而在最新的研究中，使用了兽药(Atopica, Novartis)，在一项研究中两种产品都应用了。

Analysis of efficacy

疗效分析

Two double-blinded, placebo-controlled studies, one double-blinded, prednisolone-controlled study, three prospective open studies, and two retrospective case series, reported the treatment outcome in 328 cases of FASS. In general, ciclosporin was effective in 40–100% of the cats. However, scoring systems for the lesions varied. Many studies used a validated score such as the SCORFAD,and others used the Feline Eosinophilic Granuloma, Eosinophilic Plaque, Extension and Severity Index (FEGEPESI), or a score devised as a total lesion score (TLS) describing the extent and severity on a scale from 0 to 4 for each of the major reaction patterns seen in FASS. One study used a CADESI-02 score validated for cAD. Owner-assessed pruritus was evaluated in most studies using a pVAS, yet one study used a scale from 1 to 5, and another used a scale from 1 to 10. The latter study also evaluated the lesions on a 1–10 scale . Only two studies used owner global assessments. Finally, one retrospective study did not consider pruritus or lesions, and rather evaluated the owners’ impressions of various treatments. One study was a follow-up of a double-blinded, placebo-controlled study and evaluated tapering schedules for ciclosporin in cats. During the final four weeks of that particular study, 63%, 22% and 15% of 157 cats could be maintained on twice-weekly, every other day or daily treatment, respectively. Likewise, in another open study ciclosporin could be tapered to every other day in 15% and twice weekly in 57% of the cats. Results of the various studies are listed in Table 6.

两项双盲、安慰剂对照研究、一项双盲、泼尼松龙对照研究、三项前瞻性开放研究和两项回顾性病例分析报告了328例FASS的治疗结果。总的来说，环孢素对40-100%的患猫有效。然而，病变的评分系统各不相同。许多研究使用已验证的评分表如SCORFAD,其他则使用猫嗜酸性肉芽肿、嗜酸性斑块严重程度指数(FEGEPESI),或总病变评分表(TLS)描述每个FASS病例的主要反应模式的严重程度等级从0到4。一项研究使用应用于cAD的已验证的CADESI-02评分。大多数研究宠主使用pVAS评估瘙痒，但有一项研究使用1到5的评分标准，另一项使用1到10的评分标准。后一项研究也对病变进行了1-10的评分。只有两项研究使用了宠主整体评估。最后，一项回顾性研究没有考虑瘙痒或病变，而是评估了主人对各种治疗方法的印象。其中一项研究是一项双盲、安慰剂对照研究的后续研究，评估了环孢素在猫体内的减量时间表。在这项研究的最后四周，157只猫中的63%、22%和15%患猫分别可以每周两次、隔日一次或每日一次维持治疗。同样，在另一项开放研究中，15%患猫隔日一次服用环孢素，57%患猫每周两次服用环孢素。各项研究的结果列于表6。

Ciclosporin did not affect mast cell degranulation or the early asthmatic response in A. suum-sensitised cats with induced asthma. However, in another study by the same group, ciclosporin was shown to reduce airway reactivity and remodelling after chronic antigen challenge in cats sensitised to A. suum.  Ciclosporin also was used in a cat with feline asthma and concurrent congestive heart failure and diabetes mellitus at a dosage of 4 mg/kg twice daily. Clinical signs and airway eosinophilia resolved completely within three weeks of therapy. However, thereafter the ciclosporin was replaced with inhaled fluticasone and long-term effects of the ciclosporin could not be evaluated.

环孢素对猪蛔虫过敏患猫诱发哮喘的肥大细胞脱颗粒和哮喘早期无影像。然而，在同一组的另一项研究中，环孢素被证明可以减少对猪蛔虫过敏患猫的慢性抗原刺激后的气道反应性和气道重塑。猫哮喘和并发充血性心力衰竭和糖尿病的病例也适用了环孢素，剂量为4mg/kg，每日两次。临床症状和气道嗜酸性细胞在治疗三周内完全消失。然而，此后用吸入氟替卡松取代了环孢素，且没有评估环孢素的长期疗效。

Adverse effects

副作用

In all studies, gastrointestinal signs were the most common adverse effects. In one study, vomiting, diarrhoea and/or anorexia was noted in 12 of 50 and weight loss in eight of 50 cats. Gingival hyperplasia, a known adverse effect in dogs, occurred once. In one study, vomiting occurred in 26 of 65 and diarrhoea in 13 of 65 cats. In another study, diarrhoea was more common (in five of 18) than intermittent vomiting (three of 18). In one study, the neutrophil and eosinophil cell count decreased significantly in the high-dose group, and still was within the reference range. An elevation in total bilirubin, urea and glucose also was seen in the highdose group, yet again all values were within the reference range. Nonsignificant weight loss was seen in the first three weeks, and reversed in the second three weeks of the study when the medication, initially mixed with food, was given separately orally. Cryptococcosis and toxoplasmosis developed in one and two of ten cats, respectively, in one retrospective study. In a larger study, 10 of 144 cats receiving ciclosporin had a positive Toxoplasma titre. Other adverse effects included anorexia, lethargy, sneezing and weight loss, at least one of which occurred on daily ciclosporin in 80% of cases in one report. Increased appetite and polydipsia (in one cat each) were seen in another study. In one study none of the 32 cats on glucocorticoids or ciclosporin for at least six months showed subclinical bacteriuria, when urine obtained by cystocentesis was evaluated. Although not reported in any of the cited studies, acute bullous keratopathy was significantly associated with systemic administration of ciclosporin in cats in a larger study evaluating 12 patients that had developed this disease in a population of 70,167 cats.

在所有的研究中，胃肠道症状是最常见的副作用。在一项研究中，50只猫中有12只出现呕吐、腹泻和/或厌食，50只猫中有8只体重下降。牙龈增生是犬已知的副反应，在猫曾经发生过一次。在一项研究中，65只猫中有26只会呕吐，65只猫中有13只会腹泻。在另一项研究中，腹泻(18例中的5例)比间歇性呕吐(18例中的3例)更常见。在一项研究中，高剂量组中性粒细胞和嗜酸性细胞计数明显下降，仍在参考范围内。高剂量组的总胆红素、尿素和葡萄糖也升高，但所有值都在参考范围内。在研究的前三周，体重没有显著下降，而在研究的第二周，当药物(最初与食物混合)单独口服时，体重出现下降。在一项回顾性研究中，每10只猫中分别有1只和2只感染隐球菌病和弓形体病。在一项更大规模的研究中，144只接受环孢素治疗的猫中有10只弓形虫滴度呈阳性。其他副作用包括厌食、嗜睡、打喷嚏和体重下降，在一份报告中80%的病例中每天服用环孢素至少会出现一种副作用。在另一项研究中，各有一只猫发生食欲增加和饮水增加。在一项研究中，32只猫在使用糖皮质激素或环孢素至少6个月后，没有一只表现出亚临床细菌尿。虽然没有在任何引用的研究中报道，但在一项更大的研究中，患猫急性大疱性角膜病变与全身性服用环孢素显著相关，该研究评估了在70167只猫中发生这种疾病的12名患猫。

Recommendations

建议

Based on the available evidence in a large number of cats with FASS, ciclosporin at a dose of 7 mg/kg once daily is efficacious in the treatment of reaction patterns caused by FASS (QOE 1; SOR A). In more than half of the cats, ciclosporin could be tapered from daily to twice-weekly administration. By contrast, there is insufficient evidence to recommend ciclosporin for feline asthma. As reported in dogs, gastrointestinal adverse effects are the most common. There is evidence that cats that get infected with Toxoplasma gondii while receiving ciclosporin daily develop much more severe clinical signs, or even die. By contrast, shedding of oocysts or recurrence of clinical signs was not seen in cats already infected with Toxoplasma before ciclosporin administration. Consequently, Toxoplasma antibody titres may be recommended before ciclosporin therapy and may influence the treatment decision in seronegative cats with access to outdoors or fed raw meat (QOE2; SOR B).

根据大量FASS患猫的现有证据，环孢素以7 mg/kg每日1次治疗FASS引起的反应模式有效 (QOE 1; SOR A)。在超过半数的猫中，环孢素可以从每天服用逐渐减少到每周两次服用。相比之下，没有足够的证据推荐环孢素治疗猫哮喘。据犬的报道，胃肠道副反应是最常见的。有证据表明，猫在每天服用环孢素的同时感染刚地弓形虫，会出现更严重的临床症状，甚至死亡。相比之下，已感染弓形虫的猫在服用环孢素前未出现卵囊脱落或临床症状复发。因此，在环孢素治疗之前，可能建议检测弓形虫抗体滴度，并且可能会影响血清学阴性的且有机会到户外或喂食生肉的猫的治疗决定 (QOE2; SOR B)。

Oclacitinib

奥拉替尼

Analysis of evidence

证据分析

One case report, two open prospective studies and one methylprednisolone-controlled double-blinded study reported the efficacy of oclacitinib for FASS. These included 68 cats, 48 of whom were treated with oclacitinib. In one abstract, details of the improvements were not given. The outcome measures of the other two prospective studies were a clinician-assessed lesional score, the SCORFAD and an owner-based pVAS. One study did not specify the lesion type,and the other studies included 19 cats with excoriations on the head and neck, eight cats with self-induced alopecia, four cats with eosinophilic granuloma and one cat with miliary dermatitis. Most cats presented with more than one lesion type. Seasonality was not recorded for any cat. In a randomised, placebo-controlled study, 24 cats with induced asthma experimentally sensitised to Bermuda grass received oclacitinib at 0.5 or 1.0 mg/kg twice daily for four weeks and airway inflammation was monitored. In addition, a more recent study documented a more rapid elimination of oclacitinib in the cat versus the dog, and recommended a shorter dose interval and/or higher doses of oclacitinib in cats compared to dogs.

一份病例报告、两份开放前瞻性研究和一份甲基泼尼松龙对照双盲研究报道了奥拉替尼对FASS的疗效。其中包括68只猫，其中48只接受了奥拉替尼治疗。在一份摘要中，没有给出改善详情。其他两项前瞻性研究的结果衡量指标是临床医生评估病变评分和SCORFAD，宠主进行pVAS评分。一项研究没有明确指出病变类型，其他研究包括19只头部和颈部有抓痕的猫、8只自发性脱毛的猫、4只患有嗜酸性肉芽肿的猫和1只患有粟粒性皮炎的猫。大多数猫都有一种以上的病变类型。所有患猫没有记录有季节性。在一项随机、安慰剂对照的研究中，24只对百慕大草实验室致敏诱发哮喘患猫在四周内每天两次以0.5或1.0 mg/kg剂量服用奥拉替尼，并监测呼吸道炎症反应。此外，最近的一项研究表明，与犬相比，在猫体内奥拉替尼的消除速度更快，并且建议给猫使用奥拉替尼，给药间隔更短和/或给药剂量更高。

Analysis of efficacy

疗效分析

Treatment outcome data were available for all 48 cats with FASS (see Table 7). Cats that responded to treatment were reported to do so within one month. Overall, a good response was reported at a dosage of 1 mg/kg once or twice daily. One third of the cats had a good-to-excellent response in one study. In one case report with long-term follow-up, the cat achieved long-term clinical remission while on therapy.

可见所有48只FASS患猫的治疗结果数据(见表7)。据报道，对治疗有效的猫在一个月内就会有反应。总的来说，每日1次或每日2次剂量为1mg/kg时，效果良好。在一项研究中，三分之一患猫效果良好到优秀。在一个长期随访的病例报告中，猫在治疗期间取得了长期临床缓解。

In the study evaluating the two doses of oclacitinib (0.5 or 1.0 mg/kg twice daily) in cats with experimental asthma, the percentage of eosinophils in BALF was significantly decreased compared to placebo with no difference between the two dosages. There was no significant difference between treatment groups in the effective concentration of methacholine that induced a 200% increase over baseline airway resistance.

研究评估了两种剂量的奥拉替尼(0.5或1.0mg/kg，每天两次)治疗实验室哮喘患猫，BALF中嗜酸性细胞的比例与安慰剂相比显著降低，两种剂量之间没有差异。治疗组间的甲胆碱有效浓度诱导的气道阻力比基线增加200%没有显著差异。

Adverse effects

副作用

Adverse effects were not specifically recorded in two studies, although in one study owners reported the drug to be clinically well-tolerated by all cats. In another study, at least half of the cats were monitored with complete blood counts and serum biochemistry with neutropenia seen in two, thrombocytopenia in one, increased blood ureanitrogen and creatinine in four, and increased alanine aminotransferase in three cats. In the case report monthly serum biochemistries and complete blood counts for 10 months did not show any changes. In a recent placebo-controlled safety study, oclacitinib was administered at 1 and 2 mg/kg twice daily for 28 days. Vomiting and soft stools were noted in two of 10 cats each in the high-dose group. A small increase in fructosamine concentrations was observed for both treated groups compared with placebo; however, values remained within the normal reference range. There were no differences in individual parameters in complete blood counts and biochemistry panels. In the study of cats with experimental asthma, no adverse effects were noted in the four weeks of treatment.

在两项研究中没有具体记录副作用，但在一项研究中，宠主报告说所有猫都对该药物临床耐受良好。在另一项研究中，至少有一半的猫接受了全血细胞计数和血清生化监测，其中两只猫出现了中性粒细胞减少症，一只出现了血小板减少症，四只猫的血尿素氮和肌酐增加，三只猫的丙氨酸转氨酶增加。在本病例报告中，每月的血清生化和10个月的全血细胞计数均未显示任何变化。在最近的一项安慰剂对照安全性研究中，奥拉替尼以1和2 mg/kg剂量每日两次，连续28天。在高剂量组中，10只猫中各有2只出现呕吐和软便。与安慰剂组相比，两组患猫的果糖胺浓度均有小幅增加，但是，数值仍然在正常参考范围内。在全血细胞计数和生化指标方面，单个参数没有差异。在对实验性哮喘患猫的研究中，在四周的治疗中没有发现任何副反应。

Recommendations

建议

Oclacitinib at a dosage of approximately 1 mg/kg once or twice daily was an efficacious treatment option for FASS (QOE1; SOR A). Based on the small number of cats and the short duration of most studies as well as the lack of long-term safety data and the off-label use of the drug, cats receiving oclacitinib should be monitored closely until more data are available. There also is only limited evidence for the use of oclacitinib in asthmatic cats (QOE2; SOR B) and, to the best of the authors’ knowledge, no study has evaluated this drug in naturally occurring feline asthma.

奥拉替尼剂量约为1 mg/kg，每日1次或每日2次，是FASS的有效治疗选择(QOE1; SOR A)。基于猫的数量较少，大多数研究持续时间较短，缺乏长期安全性数据和药物标示外使用，接受奥拉替尼的猫应密切监测，直到获得更多数据。也只有有限的证据表明奥拉替尼用于哮喘患猫(QOE2; SOR B)，并且，就作者所知，没有研究评估这种药物对自然发生的猫哮喘的疗效。

红蓝紫

秘鸢

2heiyanquan

南海

王超

莲子粥粥

梁倩

笼中红细胞

王科美