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Wednesday, March 21, 2018

妊娠紋 伴隨 urticarial皮膚癢疹 與mast cell/MMP-9過度反應有關: Anemarrhena & Angelica PEG-Lyophilized Sérum-élastique paire 潛力


妊娠期常見的皮膚異常症狀與治療 日期:2016/02/25台中榮總婦產部總醫師  黃佩真 期待、迎接新生命的到來,對大部分懷孕的媽媽來說,是充滿喜樂與美好的,然而,因為孕程生理的變化,可能造成準媽媽們在身體與心理上的總總變化,特別是外貌的改變,可能會讓部分的媽媽變得焦慮、擔心。懷孕過程中,常見的皮膚及結締組織改變包括有色素沉澱、血管變化以及毛髮問題等;其中色素沉澱是最常見的,常發生的位置包括了乳暈、腹部中間的黑線 (linea nigra )、外陰部或大腿內側,另外,兩頰的孕斑 (mask of pregnancy)也是常見色素沉澱的一種,多半呈現不規則狀、顏色不均勻的斑塊,特別是原來皮膚顏色較深的位置較易發生,常曬太陽的人也比較容易長,所以適當的作好防曬有其必要,孕斑大部份在生產完後一年內會漸漸消退,如果產後孕斑一直不退,可以考慮使用A酸、類固醇、果酸或是雷射治療。腿部、陰部、痔瘡等靜脈曲張、發炎是很常見的血管變化,除了影響美觀、有時也會伴隨有疼痛的困擾,休息時將腿部抬高、平時穿著彈性襪、避免久坐或站,都是預防或減輕症狀的妙招。懷孕過程及產後,頭髮會變粗、毛燥或掉髮(特別是產後24個月的休止期),甚至出現禿頭的問題。這些都是孕(產)婦媽媽受到荷爾蒙影響所可能產生的正常生理變化,大部份的媽媽都可以在產後半年到一年間逐漸恢復正常,倒也不必過於擔心。除了上述正常生理變化引起的皮膚改變外,也有一些是與懷孕相關,僅發生在懷孕或產媷期的、較不正常的皮膚變化或疾病。仔細的病史詢問,包括懷孕週數、次數或胎數、前次懷孕之相關症狀或家族史等,加上詳細的理學檢查可增加診斷之正確性,必要時應至皮膚科接受進一步的診斷與治療。這些疾病包括如下:

1. 妊娠類天皰瘡 (Pemphigoid gestationis, PG) 又稱為妊娠皰疹 (herpes gestationis),一種罕見的自體免疫疾病,在妊娠中期、晚期出現,最先由腹部出劇烈搔癢的水泡及紅疹,之後會快速擴散,四肢與手掌、腳掌可能也會有病兆出現,但一般不會侵犯到臉部與粘膜。大部分的產婦在生產後數週至數月內自然復原,但也有些產婦會暫時惡化。至於胎兒部分則可能因為免疫反應造成的胎盤功能不良,造成胎兒早產或低出生體重。輕症患者可處方抗組織胺或外用類固醇製劑來改善症狀,嚴重時則需要口服類固醇的治療。  

2. 妊娠搔癢性蕁麻疹樣丘疹及斑塊 (Pruritic urticarial papules and plaques of pregnancy, PUPPP)由於皮疹可呈粒狀、塊狀或水泡樣等多種形態,故又稱為妊娠多形疹(polymorphic eruption of pregnancy, PEP),通常只發生在初產婦的懷孕末期,為最常見於懷孕期的皮膚疾病。症狀一般是從環繞肚臍的妊娠紋中出現癢疹,一般少見於肚臍、臉部或手腳掌之皮膚,也少見摳抓痕,病兆在產後自然消退、很鮮少發生在下一胎。多胞胎妊娠、母體或胎兒異常體重增長是此病症出現的危險因子,但確切的病因仍然沒有定論;本病相當良性,罕見母體或胎兒之嚴重合併症,因此只需給予症狀治療。

3. 皮膚癢疹(Prurigo of pregnancy) 皮膚癢疹是最常見的懷孕相關皮膚疾症,從懷孕第四個月到第九個月皆可能發生,主要是小丘疹分佈在四肢近端,尤其是關節彎曲側,與軀幹上部。有人認為荷爾蒙變化、乾燥、外來物刺激,例如妊娠霜,或是肝內膽汁鬱積等皆可能造成類似的搔癢症狀。過去曾是異位性體質的人,也容易在懷孕時出現皮膚癢疹。臨床症狀在生產後會迅速緩解,雖然發炎後的色素沉著會持續一段時間,但本病較不會復發,且截至目前為止,對於胎兒並無已知的影響性。治療一般是使用局部的類固醇藥膏做症狀的緩解。

4. 膿皰型乾癬 Pustular psoriasis of pregnancy為極罕見的妊娠皮膚疾病,多發生在第三妊娠期,產後自然痊癒。初期可在鼠蹊、腋下或頸部發現不具癢感的紅斑,其中散佈細小的無菌性膿皰,隨後病灶由新的膿皰包圍其邊緣向外擴散,粘膜或指甲下也可能受到侵犯,此時舊的膿皰會結痂、脫皮或膿痂疹樣的變化。實驗室檢查可發現白血球數或紅血球沈降率上昇,而血鈣及白蛋白則暫時下降,當臨床上合併有發燒的症狀時,必須與感染症鑑別診斷。可能會因為疾病造成胎盤功能不良、而增加胎兒致病或死亡的風險。嚴重時需以口服類固醇來治療,另外要注意皮膚與系統性感染症導致敗血症,或低血鈣合併癲癇等併發症的發生。

5. 孕期肝內膽汁鬱積(Intrahepatic cholestasis of pregnancy, ICP又稱為懷孕癢疹(prurigo gravidarum)其特色為全身癢感但無原發性皮膚病灶。多發生高齡產婦或多產婦的末期妊娠,初期可能只有局部或夜間癢感。目前對於ICP之發生原因沒有定論,但可能造成孕婦、甚至胎兒嚴重的併發症,例如可能增加孕婦膽結石的發生率,也可能因為胎盤缺氧而增加胎兒窘迫、死產或早產的風險,嚴重時可能合併孕婦維生素K缺乏,需小心子宮或顱內出血的危險。治療首重控制癢感,可使用保濕乳液、口服抗組織胺或局部止癢劑等來改善症狀,雖然可以嘗試以cholestyramineursodeoxycholic acid改善較嚴重膽汁鬱積,但臨床安全性資料仍不充份,處方時必須小心。上述的懷孕相關皮膚疾症中,有些可能會造成嚴重的胎兒影響,例如妊娠類天皰瘡、膿皰型乾癬,一旦臨床上出現了疑似診斷的個案,應該轉介到皮膚科做進一步的切片診斷,給予適當的產前照護與治療,以避免嚴重併發症的發生。其他如皮膚癢疹或妊娠搔癢性蕁麻疹樣丘疹及斑塊等,雖然較為常見,但通常對胎兒沒有影響。大部分的準媽媽會因為害怕藥物對於胎兒造成副作用,而隱忍這些皮膚症狀,但目前醫學上用以治療妊娠搔癢症的藥物,都是相當安全的。建議一旦出現了相關的皮膚症狀,還是應該儘快就醫,經由醫生仔細的檢查、做出正確的診斷、給予安全的用藥,才能確保胎兒健康,讓準媽媽們舒適地度過懷孕的階段。

During pregnancy, the maternal organism is under the influence of tremendous endocrine as well as immunological changes as an adaptation to the implanted and developing fetus. In most cases, the maternal adaptations to pregnancy ensure both, the protection against harmful pathogens and the tolerance toward the growing semi-allogeneic fetus. However, under certain circumstances the unique hormonal milieu during pregnancy is causative of a shift into an unfavorable direction. Of particular importance are cellular disorders previous to pregnancy that involve cell types known for their susceptibility to hormones. One interesting cell type is the mast cell (MC), one of the key figures in allergic disorders. While physiological numbers of MCs were shown to positively influence pregnancy outcome, at least in mouse models, uncontrolled augmentations in quantity, and/or activation can lead to pregnancy complications. Women that have the desire of getting pregnant and been diagnosed with MC mediated disorders such as urticaria and mastocytosis or chronic inflammatory diseases in which MCs are involved, including atopic dermatitis, asthma, or psoriasis, may benefit from specialized medical assistance to ensure a positive pregnancy outcome. In the present review, we address the course of pregnancy in women affected by MC mediated or associated disorders. Neutrophils, mast cells and macrophages are the predominant source of matrix metalloproteinase (MMP)-9. Chronic exposure of human skin to solar ultraviolet (UV) radiation causes photoaging. Naturally occurring phytochemicals are known to have anti-photoaging effects. The effect of mangiferin isolated from Anemarrhena asphodeloides on wrinkle formation, skin thickness, and changes in collagen fibers in hairless mice. The in vitro effects and possible mechanism of mangiferin on UVB irradiation were determined in human keratinocyte (HEKa) cells. In vitro results showed that mangiferin reduced UVB-induced matrix metalloproteinase (MMP)-9 protein expression and enzyme activity and subsequent attenuation of UVB-induced phosphorylation of mitogen-activated protein kinase kinase1 (MEK) and extracellular signal-regulated kinase (ERK). In the in vivo studies, mangiferin inhibited UVB-induced mean length and mean depth of skin wrinkle based on skin replica, epidermal thickening, and damage to collagen fiber. Taken together, these results indicate that mangiferin exerts anti-photoaging activity in UVB-irradiated hairless mice by regulating MMP-9 expression through inhibition of MEK and ERK. In addition, active polysaccharide from Angelica sinensis (Oliv.) Diels is identified as one of the important and active components in terms of antitumor activity, immunoregulatory effect, radioprotective effect, and inhibition of platelet aggregation. Polysaccharide Enriched Glycopid Lyophilized, PEG-Lyophilized: Sérum-élastique paire could inhibit the activation of mast cells via suppressing the releases of proinflammatory cytokines allergic mediators, Gab2/PI3-K/Akt and Fyn/Syk pathways.  


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