用异维甲酸治疗痤疮时须警惕眼病

以色列特拉维夫医学中心眼科的Meira Neudorfer博士及其同事指出，在因痤疮而开具异维甲酸处方时，应同时处方眼部润滑剂。

既往研究已表明，使用异维甲酸与眼部异常风险增加相关，停药后多数可逆转。不良事件的风险增高与异维甲酸诱导睑板腺功能异常的生物学效应有关。这项大型回顾性研究纳入了14,682名青少年和年轻成年异维甲酸新使用者，并设置了2个年龄和性别匹配配的对照组。第一个对照组包括14,682例痤疮患者，但从未接受过异维甲酸治疗；第二个对照组则包含14,682例从未患痤疮也从未接受过异维甲酸治疗的患者(Arch. Dermatol. 2012;148:803-8)。数据来自2000年1月1日~2007年12月31日期间特拉维夫Maccabi医疗保健服务健康维护组织的电子数据库。在以色列，建议的异维甲酸使用剂量为累计剂量120~150 mg/kg。

结果显示，在治疗第1年内，异维甲酸治疗组、未接受异维甲酸治疗的痤疮患者组和非痤疮患者组的眼部不良事件发生率分别为13.8%、9.6%和7.1%。最常见的不良事件为结膜炎、麦粒肿、霰粒肿、睑缘炎、眼痛和眼干。异维甲酸治疗组、未接受异维甲酸治疗的痤疮患者组和非痤疮患者组分别有6.7%、3%和2.4%的患者被诊断为眼部炎性疾病，并分别有1.0%、0.5%和0.4%的患者发生眼部结构性疾病。急性结膜炎是最常见的不良预后，异维甲酸治疗组发生率为未接受异维甲酸治疗的痤疮患者组的1.7倍(4.0% vs. 2.4%)，非痤疮患者组发生率仅为1.9%。研究者还发现，女性患者眼部不良事件的发生率增高，这与“女性较多使用医疗保健服务的现状相一致”。

急性结膜炎

研究者指出，“这项研究的结果凸显了一级和二级预防的重要性”，在患者首次接受异维甲酸治疗后约4个月，应进行1次眼科随访。“当使用异维甲酸的患者发现眼部问题时，眼科医生应明确症状发生的时间，并在治疗仍无法阻止症状进展或症状持续存在的情况下，考虑停用异维甲酸。”

研究者披露无相关利益冲突。

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By: NASEEM S. MILLER, Internal Medicine News Digital Network

When prescribing isotretinoin for acne, ocular lubricants should also be prescribed, according to Dr. Meira Neudorfer and colleagues.

The researchers, who conducted a large, retrospective study of young adults who received prescriptions for isotretinoin for acne, also recommended that "a follow-up visit to the ophthalmologist should be scheduled about 4 months after the first dispensed isotretinoin prescription."
 
The recommendations come from their study findings which compared 14,682 adolescents and young adults who were new users of isotretinoin, with two age- and sex-matched control groups. The first comparison group of 14,682 patients had acne, but the patients were never treated with isotretinoin; and the second comparison group of 14,682 patients did not have acne and were never treated with isotretinoin (Arch. Dermatol. 2012;148:803-8).

Isotretinoin use was associated with an increased risk for developing ocular disorders – an attribution established by previous studies – which are mostly reversible once the therapy is discontinued. The elevated risk of adverse events is attributed to the biological effect of isotretinoin, inducing meibomian gland dysfunction, wrote Dr. Neudorfer of the department of ophthalmology at Tel Aviv Medical Center, and colleagues.

Data were collected from the electronic database of the health maintenance organization, Maccabi Healthcare Services, Tel Aviv, between January 1, 2000, and December 31, 2007. The recommended dose of isotretinoin in Israel is a cumulative dose of 120-150 mg/kg.

During the first year of treatment, 13.8% of the isotretinoin group experienced adverse ocular events, compared with 9.6% of the isotretinoin-naïve patients, and 7.1% of the acne-free patients. The most common adverse events were conjunctivitis, hordeolum, chalazion, blepharitis, eye pain, and dry eye, according to the study.

Inflammatory ocular diseases were diagnosed in 6.7% of the isotretinoin group, 3% of the isotretinoin naive group, and 2.4% of the acne-free group. Structural ocular diseases were observed in 1.0%, 0.5% and 0.4% of the three groups, respectively.

Acute conjunctivitis was the most frequent prognosis and occurred 1.7 times more frequently in the isotretinoin group than in the isotretinoin-naive group (4.0% vs. 2.4%, respectively). In the acne-free group, the occurrence was 1.9%.

The study also found an increased incidence of ocular adverse events among female patients, which was "in line with the known greater use of health care services by women," the researchers noted.

The authors listed several limitations to the study. For instance, patients with acne experienced more ocular disease than did the general population because of the disease itself, so "it is reasonable to assume that the ocular disturbance is directly associated with the degree of acne severity," they wrote. There was also a lack of data on contact lens use, something that could lead to complications and influence the association between use of isotretinoin and ocular disease.

"The study results underscore the importance of primary and secondary prevention measures," the authors concluded. "When patients taking isotretinoin are seen with ocular problems, ophthalmologists should ascertain the timing of the onset of symptoms and consider discontinuation of the drug if the symptoms progress or persist despite treatment."

The authors did not report having any conflicts of interest.