皮膚搔癢症：機制與治療

Pruritus：Mechanism and Treatment

柯玫如(Mei-Ju Ko)

指導教授 ： 紀秀華 ； 張智芬

國立臺灣大學/醫學院/臨床醫學研究所/博士(2013年)

https://doi.org/10.6342/NTU.2013.00211

摘要

搔癢是皮膚疾病的主要症狀，也常是全身性疾病的表現。皮膚搔癢症可引起嚴重不適、焦慮、抑鬱、睡眠問題、皮膚損害，並影響生活品質。

廣泛性搔癢症，定義為大範圍的皮膚搔癢但沒有原發性皮疹，發生於約3％到50％的糖尿病患。較早的研究報告指出糖尿病婦女有較高的陰部搔癢症，但罹患廣泛性搔癢症與糖化血色素並沒有相關。最近的研究則顯示，糖尿病患者比起非糖尿病患者有較高的比率發生不明原因軀幹部位的搔癢，並與糖尿病的多發神經病變相關。

我們執行一橫斷式研究，由糖尿病照護系統招募第2型糖尿病的患者。由皮膚科醫師執行皮膚檢查，並使用詳細的問卷，包括視覺模擬評分法，評估搔癢的特性及強度。最後，利用羅吉斯迴歸分析，研究飯後血糖、飯前血糖和糖化血紅素與廣泛性搔癢症之關係。

這個研究招募了385位糖尿病患者，106位(27.5％)患有廣泛性搔癢症。其中，因為搔癢，24.5％有入睡困難，15.1％有睡眠障礙，9.5％需要助眠劑。第2型糖尿病患者若飯後血糖較高，患有廣泛性搔癢症的風險也較高〔OR=1.41（95％ C.I.：1.05–1.90）, P=0.02〕。

研究結果顯示第2型糖尿病患者之廣泛性搔癢症與飯後血糖控制相關。此結果可提醒臨床醫師關注糖尿病患者的搔癢症狀，並使患者更有動機做好血糖控制。

尿毒性搔癢症是慢性腎臟病患者常見且困擾的症狀，接受長期透析約有百分之四十至九十的病人有此症狀。至今，尿毒性搔癢症的機制尚不清楚。許多尿毒性皮膚搔癢症患者有極長之病程，且搔癢強度過程中可能會有高低，但缺乏相關的縱向追蹤研究。

為了解決這個問題，我們執行了一項前瞻性、追蹤5年的世代研究，探討血液透析患者搔癢強度加重或緩解的預測因子。此縱向追蹤研究，透過change score analysis考慮每個共變項的變化，分析搔癢強度、代謝概況以及透析充分性的關係。並使用廣義加法模型（generalized additive models)及receiver operating characteristic曲線決定透析廓清率（Kt/V）的最佳閥值。

共111例患者完成這項研究。線性迴歸分析顯示，調整基礎搔癢強度和干擾因子後，較低之透析廓清率（Kt/V）及使用低透量透析器與搔癢加重有顯著的相關。廣義加法模型及receiver operating characteristic曲線建議之最佳Kt/V閥值皆約為1.5。此閥值略高於目前以減少死亡率為目標的臨床準則之數值。研究結果顯示，Kt/V值高於當前的標準，雖不能進一步降低死亡率，但可能可以提高生活品質。這也暗示著致癢物質的清除可能影響搔癢的強度。

尿毒性搔癢症的治療方式至今仍是相當有限。寬頻紫外光B光照療法已被證實可有效治療尿毒性搔癢症。因為窄頻紫外光B光照療法在乾癬的治療更為有效，近年來，逐漸以窄頻紫外光B光照療法取代寬頻紫外光B光照療法。但關於窄頻紫外光B光照療法對尿毒性搔癢症的研究非常少。

因此，我們執行了一個單盲、隨機控制之臨床試驗，評估窄頻紫外光B光照療法對減輕尿毒性搔癢症之療效。納入的受試者為大於18歲，慢性腎臟病第3期至第5期或第5期D之成年人。受試者之搔癢強度須以視覺模擬評分法評估超過5分，搔癢病程超過2個月，並對口服抗組織胺及局部藥物治療反應不佳。治療組接受全身窄頻紫外光B光照療法，每周3次，共6周。起始劑量由210 mJ/cm2逐漸增加。控制組接受相同時間的長波長紫外光A光，劑量約1-6 J/cm2。治療前及第6週使用問卷評估皮膚搔癢的詳細情形，並且每週評估皮膚搔癢的強度至第12週。

治療組、控制組患者搔癢的程度在治療及追蹤期間皆有顯著的進步。然而，兩組間並無統計學上顯著的差異。使用效力更佳的統計方式分析，顯示搔癢的程度在治療結束時(第6週)及追蹤時(第10、12週)，窄頻紫外光B光照療法比起控制組有統計上顯著的差異，但其效果有限。相較於治療前，第6週時治療組搔癢影響之體表面積有顯著的進步，但控制組則無此效果。治療組及控制組在治療前及第6週時，關於睡眠品質的評估，沒有達到顯著的差異。

此研究中，我們沒有發現窄頻紫外光B光照療法比起控制組，對尿毒性搔癢症有顯著的療效。這不同於前人的研究發現寬頻紫外光B光照療法對尿毒性搔癢症有效。因此，雖然窄頻紫外光B光照療法已證明比寬頻紫外光B光照療法更有效地治療乾癬，其優異的效果無法直接推論於其他光照治療有效的皮膚疾病，如：尿毒性搔癢症。

關鍵字

癢 ； 高血糖 ； 血糖控制 ； 糖尿病 ； 尿毒性搔癢症 ； 透析充分性 ； 透析廓清率 ； 光照療法 ； 窄頻紫外光

並列摘要

Pruritus is the dominant symptom of skin disease and a frequent manifestation of systemic disease. It causes serious discomfort, anxiety, depression, sleeping disorders, considerable skin damagend and has substantial effects on quality of life.

We conducted a cross-sectional study to investigate the association of glycemic control with generalized pruritus in type 2 diabetes. A total of 385 patients with type 2 diabetes who attended the diabetes care system underwent cutaneous examination by a dermatologist. A detailed interview questionnaire including visual analogue scale was used to assess various characteristics and the intensity of pruritus.

Generalized pruritus was noted in 27.5% of the diabetic patients. As a result of pruritus, 24.5% of the patients had difficulties in falling asleep, 15.1% had disturbance of sleep, and 9.5% needed soporifics. Patients who had a higher postprandial glucose level had a higher probability of having generalized pruritus [OR=1.41 (95% C.I.: 1.05–1.90), P=0.02] in type 2 diabetic patients.

We found generalized pruritus in patients with type 2 diabetes mellitus is associated with PC glucose control. This finding arouses the physicians to pay more attention to pruritus in diabetic patients and to motivate the patient for better blood glucose control.

Uremic pruritus is also one of the most common and bothersome symptoms in patients with chronic kidney disease, with approximately 40-90% of patients on long-term maintenance dialysis suffering from this problem. To date, the mechanisms of uremic pruritus remain poorly characterized.

We conducted a prospective cohort study of patients with maintenance hemodialysis in the hemodialysis center. Patient demographic and clinical characteristics, laboratory parameters, dialysis adequacy (assessed by Kt/V), and pruritus intensity were recorded at baseline and follow-up. Change score analysis of the difference score of VAS between baseline and follow-up was performed using multiple linear regression models.

A total of 111 patients completed the study. Linear regression analysis showed that lower Kt/V and use of low-flux dialyzer were significantly associated with the aggravation of pruritus after adjusting for the baseline pruritus intensity and a variety of confounding factors. The optimal threshold value of Kt/V for pruritus was 1.5 suggested by both generalized additive models and receiver operating characteristic analysis.

The cut-off value of 1.5 for Kt/V suggested by our study for pruritus is slightly above the target levels reducing mortality recommended in clinical practice guidelines, which not only implies that a Kt/V higher than the current standard may not further improve survival but may improve the quality of life, but also indicates that the clearance of pruritogenic substances could influence the intensity of pruritus.

The therapeutic options for uremic pruritus are limited and unsatisfactory. Broad band ultraviolet B phototherapy has been demonstrated to be effective in the treatment of uremic pruritus in previous studies. Recently there is a trend of replacing BB-UVB phototherapy units with narrowband ultraviolet B (NB-UVB) units, as studies have demonstrated that NB-UVB is more efficacious in the treatment of psoriasis. However, studies regarding NB-UVB phototherpy for uremic pruritus are rare.

A single blinded, randomized control trial was conducted to investigate the efficacy of NB-UVB phototherapy in uremic pruritus. Eligible participants were adults older than 18 years old, with CKD stage 3 to 5 and 5D. Patients with pruritus of visual analogue scale score over 5, itching duration of more than 2 months, and refractory to oral antihistamines and topical emollients were enrolled. The treatment group received NB-UVB phototherapy 3 times per week for 6 weeks. The dose of NB-UVB started from 210 mJ/cm2 and was increased by 10% at each time. The control group received time-matched exposures to long-wave ultraviolet light (UVA).Visual analogue scale score was evaluated weekly for pruritus intensity for 12 weeks. The characteristics of pruritus were also assessed by a questionnaire at baseline and after 6-week phototherapy.

Both NB-UVB and control groups have significant and comparable improvement in the pruritus intensity VAS scores during the period of phototherapy and follow-up. Compared to control group, the NB-UVB group showed a significant improvement in the involved body surface area affected by pruritus (p = 0.006), but not in sleep quality. More detailed regression and estimating analysis revealed that the patients in the NB-UVB group had lower pruritus intensity at week 6, week 10, and week 12. This may indicate a beneficial difference at certain time points, but the effect seems marginal.

NB-UVB phototherapy does not show a significant effect in reducing pruritus intensity compared to control group for refractory uremic pruritus. This finding may imply that although NB-UVB has been demonstrated to be more effective than BB-UVB for the treatment of psoriasis, its superior effect should not be directly extrapolated to other potential phototherapy-responsive dermatoses, such as uremic pruritus in this study.

並列關鍵字

Itching ； Pruritus ； Hyperglycemia ； Glycemic Control ； Diabetes Mellitus ； Uremic pruritus ； Dialysis adequacy ； Kt/V ； Phototherapy ； Narrowband UVB

參考文獻

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Ada, S., Seckin, D., Budakoglu, I., and Ozdemir, F.N. (2005). Treatment of uremic pruritus with narrowband ultraviolet B phototherapy: an open pilot study. J Am Acad Dermatol 53, 149-151.

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