郝曉軍 校譯 尖峰眼科

氯喹/羥基氯喹中毒

【癥狀】

博亿娱乐 視力下降，色覺異常，暗適應困難。

【主要體征】

1、牛眼樣黃斑:環形的脫色素區，周圍被色素沉著環包圍。

2、中心凹反光消失。

【其他體征】

黃斑區色素增多，動脈變細，血管鞘，周邊色素沉著，色覺下降，視野異常(中心、旁中心或周邊暗點)。視網膜電圖和眼電圖異常，暗適應正常。角膜可見螺紋狀混濁。

博亿娱乐 【出現中毒反應所需要的劑量】

氯喹，累積劑量超過300g。

羥基氯喹，如Plaquenil，每日服用超過750mg，連服數月至數年。

博亿娱乐 注： 有學者認為，若氯喹每日劑量小于4.4mg/kg，羥基氯喹小于7.7mg/kg，則不會發生視網膜病變。

【牛眼樣黃斑病變的鑒別診斷】

1、視錐細胞營養不良  有家族史，一般發病年齡在30歲以下，嚴重畏光，明適應視網膜電圖異常或記錄不到。參見本章第二十九節視錐細胞營養不良。

博亿娱乐 2、Stargardt病    有家族史，一般發病年齡在25歲以下，眼底后極和中周部可見黃白色斑點。參見本章第三十節Stargardt病(眼底黃色斑點癥)。

博亿娱乐 3、年齡相關性黃斑變性    玻璃膜疣，色素團和萎縮灶，可有或無視網膜色素上皮脫離或視網膜感覺層脫離。參見本章第十六節非滲出性（干性）年齡相關性黃斑變性和第十七節新生血管性或滲出性(濕性)年齡相關性黃斑變性。

4、Batten病和Spielmeyer-Vogt綜合征   色索性視網膜病變，癲癇發作，共濟失調和進行性癡呆。參見本章第三十節Stargardt病(眼底黃色斑點癥)。

【治療】

若出現中毒表現，則停止服藥。

【基本檢查】

博亿娱乐 對于長期用藥的患者應預先制定檢查計劃。

博亿娱乐 1、視力檢查。

博亿娱乐 2、眼底檢查。

博亿娱乐 3、眼底后極部照相。

4、視野，推薦自動視野計，如Humphery，Octopus,使用或不使用紅色視標。

5、色覺檢查，推薦Farnsworth-Munsell 100色彩試驗。

6、多焦視網膜電圖檢查。

【隨訪】

每6月1次。

注：一旦出現眼部毒性，即使停止服藥，通常癥狀也不會消退。事實上，即使停用氯喹或羥基氯喹，仍可形成新的毒性反應，同時，舊的毒性反應仍可進展。

11.32 Chloroquine/Hydroxychloroquine Toxicity

Symptoms

博亿娱乐 Decreased vision, abnormal color vision, difficulty adjusting to darkness.

Signs

博亿娱乐 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

博亿娱乐 Chloroquine: More than 300 g total cumulative dose.

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

Note

博亿娱乐 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.

博亿娱乐 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.

博亿娱乐 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.

博亿娱乐 Batten disease and Spielmeyer–Vogt syndrome: Pigmentary retinopathy, seizures, ataxia, and progressive dementia. See 11.30, Stargardt Disease (Fundus Flavimaculatus).

Treatment

博亿娱乐 Discontinue the medication if signs of toxicity develop.

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

Visual acuity.

Ophthalmoscopic examination.

博亿娱乐 Posterior pole fundus photographs.

博亿娱乐 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

博亿娱乐 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.