氯喹/羟基氯喹中毒

郝晓军 校译 尖峰眼科

氯喹/羟基氯喹中毒

【症状】

视力下降，色觉异常，暗适应困难。

【主要体征】

1、牛眼样黄斑:环形的脱色素区，周围被色素沉着环包围。

2、中心凹反光消失。

【其他体征】

黄斑区色素增多，动脉变细，血管鞘，周边色素沉着，色觉下降，视野异常(中心、旁中心或周边暗点)。视网膜电图和眼电图异常，暗适应正常。角膜可见螺纹状混浊。

【出现中毒反应所需要的剂量】

氯喹，累积剂量超过300g。

羟基氯喹，如Plaquenil，每日服用超过750mg，连服数月至数年。

注： 有学者认为，若氯喹每日剂量小于4.4mg/kg，羟基氯喹小于7.7mg/kg，则不会发生视网膜病变。

【牛眼样黄斑病变的鉴别诊断】

1、视锥细胞营养不良  有家族史，一般发病年龄在30岁以下，严重畏光，明适应视网膜电图异常或记录不到。参见本章第二十九节视锥细胞营养不良。

2、Stargardt病    有家族史，一般发病年龄在25岁以下，眼底后极和中周部可见黄白色斑点。参见本章第三十节Stargardt病(眼底黄色斑点症)。

3、年龄相关性黄斑变性    玻璃膜疣，色素团和萎缩灶，可有或无视网膜色素上皮脱离或视网膜感觉层脱离。参见本章第十六节非渗出性（干性）年龄相关性黄斑变性和第十七节新生血管性或渗出性(湿性)年龄相关性黄斑变性。

4、Batten病和Spielmeyer-Vogt综合征   色索性视网膜病变，癫痫发作，共济失调和进行性痴呆。参见本章第三十节Stargardt病(眼底黄色斑点症)。

【治疗】

若出现中毒表现，则停止服药。

【基本检查】

对于长期用药的患者应预先制定检查计划。

1、视力检查。

2、眼底检查。

3、眼底后极部照相。

4、视野，推荐自动视野计，如Humphery，Octopus,使用或不使用红色视标。

5、色觉检查，推荐Farnsworth-Munsell 100色彩试验。

6、多焦视网膜电图检查。

【随访】

每6月1次。

注：一旦出现眼部毒性，即使停止服药，通常症状也不会消退。事实上，即使停用氯喹或羟基氯喹，仍可形成新的毒性反应，同时，旧的毒性反应仍可进展。

11.32 Chloroquine/Hydroxychloroquine Toxicity

Symptoms

Decreased vision, abnormal color vision, difficulty adjusting to darkness.

Signs

Critical. Bull's-eye macula (a ring of depigmentation surrounded by a ring of increased pigmentation), loss of the foveal reflex.

Other. Increased pigmentation in the macula, arteriolar narrowing, vascular sheathing, peripheral pigmentation, decreased color vision, visual field abnormalities (central, paracentral, or peripheral scotoma), abnormal ERG and EOG, and normal dark adaptation. Whorl-like corneal changes also may be observed.

Dosage Usually Required to Produce Toxicity

Chloroquine: More than 300 g total cumulative dose.

Hydroxychloroquine (e.g., Plaquenil): More than 750 mg/day taken over months to years.

Note

Some believe that retinopathy will not develop if the daily dose is kept at less than 4.4 mg/kg/day of chloroquine and 7.7 mg/kg/day of hydroxychloroquine.

Differential Diagnosis of Bull's-Eye Maculopathy

Cone dystrophy: Family history, usually <30 years of age, severe photophobia, abnormal to nonrecordable photopic ERG. See 11.29, Cone Dystrophies.

Stargardt disease: Family history, usually <25 years of age, may have white–yellow flecks in the posterior pole and midperiphery. See 11.30, Stargardt Disease (Fundus Flavimaculatus).

ARMD: Drusen; pigment clumping and atrophy and detachment of the RPE or sensory retina may or may not occur. See 11.16, Nonexudative (Dry) Age-Related Macular Degeneration and 11.17, Neovascular or Exudative (Wet) Age-Related Macular Degeneration.

Batten disease and Spielmeyer–Vogt syndrome: Pigmentary retinopathy, seizures, ataxia, and progressive dementia. See 11.30, Stargardt Disease (Fundus Flavimaculatus).

Treatment

Discontinue the medication if signs of toxicity develop.

Baseline Work-up For patients in whom long-term treatment is anticipated.

Visual acuity.

Ophthalmoscopic examination.

Posterior pole fundus photographs.

Visual field, preferably automated (e.g., Humphrey, Octopus, with or without red test object).

Consider color vision testing, preferably Farnsworth–Munsell 100-hue test.

Consider multifocal ERG.

Follow-Up

Every 6 months.

Note

Once ocular toxicity develops, it usually does not regress even if the drug is withdrawn. In fact, new toxic effects may develop, and old ones may progress even after the chloroquine/hydroxychloroquine has been discontinued.