Levy Britt J, Linder Keith E, Olivry Thierry
Department of Clinical Sciences, College of Veterinary Medicine, NC State University, 1060 William Moore Drive, Raleigh, NC, 27607, USA.
Department of Population Health and Pathobiology, College of Veterinary Medicine, NC State University, 1060 William Moore Drive, Raleigh, NC, 27607, USA.
Vet Dermatol. 2019 Jun;30(3):201-e63. doi: 10.1111/vde.12743. Epub 2019 Apr 21.
Ischaemic dermatopathy represents a heterogenous and poorly-characterized canine syndrome that is often refractory to conventional immunosuppression. Janus-kinase inhibitors (JAKinibs) are used for the treatment of various human autoimmune diseases, including dermatomyositis. Oclacitinib is a generally well-tolerated, veterinary-approved, nonselective JAKinib that has therapeutic potential as an immunosuppressant.
HYPOTHESIS/OBJECTIVES: To describe four cases of treatment refractory juvenile-onset ischaemic dermatopathy that rapidly and durably responded to oclacitinib administration.
Four mixed-breed dogs, three 9-month-old male littermates and one 6-month-old female, were presented for generalized patchy alopecia, scarring and ulcerative dermatitis. Microscopic skin lesions were consistent with a severe ischaemic dermatopathy.
A complete remission of skin lesions could not be achieved in any dog with glucocorticoids alone, nor when these were combined with adjuvant immunosuppressants. Oclacitinib treatment was then initiated at the dosage of 0.4-0.7 mg/kg twice daily, along with a tapering regimen of oral prednisolone.
A full clinical remission was achieved within four weeks of starting this combination therapy, with prednisolone being stopped within eight weeks thereof. Remission was maintained in two dogs with lower doses or dosing frequencies of oclacitinib, whereas the two others required persistent twice daily administration of this JAKinib.
Oclacitinib was a useful immunosuppressive adjuvant to oral glucocorticoids for the treatment of refractory or severe cases of ischaemic dermatopathy in these four dogs. Such observation warrants further studies of the safety, efficacy and mechanism of action of oclacitinib as an immunosuppressant.
缺血性皮肤病是一种异质性且特征描述不足的犬类综合征，通常对传统免疫抑制治疗无效。Janus激酶抑制剂（JAK抑制剂）用于治疗包括皮肌炎在内的多种人类自身免疫性疾病。奥克拉替尼是一种普遍耐受性良好、经兽医批准的非选择性JAK抑制剂，具有作为免疫抑制剂的治疗潜力。
假设/目标：描述4例难治性幼年型缺血性皮肤病病例，这些病例对奥克拉替尼给药迅速且持久地产生反应。
4只混种犬，3只9月龄雄性同窝幼犬和1只6月龄雌性犬，因全身性斑片状脱毛、瘢痕形成和溃疡性皮炎就诊。皮肤微观病变与严重缺血性皮肤病一致。
单独使用糖皮质激素或与辅助免疫抑制剂联合使用时，任何一只犬均无法实现皮肤病变的完全缓解。然后开始以0.4 - 0.7mg/kg的剂量每日两次给予奥克拉替尼，并同时逐渐减少口服泼尼松龙的剂量。
开始这种联合治疗后4周内实现了完全临床缓解，泼尼松龙在8周内停用。2只犬使用较低剂量或较低给药频率的奥克拉替尼维持缓解，而另外2只犬需要持续每日两次给予这种JAK抑制剂。
奥克拉替尼是口服糖皮质激素治疗这4只犬难治性或严重缺血性皮肤病的有用免疫抑制辅助药物。这一观察结果值得进一步研究奥克拉替尼作为免疫抑制剂的安全性、疗效和作用机制。
