抗疟药在皮肤科的临床应用及其监测

抗疟药治疗皮肤病的历史可回朔到Ｐａｖｎｅ于 1894年用奎宁和Ｐａｇｅ于 195 1年用阿的平治疗红斑狼疮 (ＬＥ) ,目前已广泛用于治疗ＬＥ、多形性日光疹和迟发性皮肤卟啉病 (ＰＣＴ)等〔1～ 5〕。皮肤科目前应用的主要为氯喹 (ｃｈｌｏｒｏｑｕｉｎｅ ,Ａｒ ａｌｅｎ)、羟氯喹 (ｈｙｄｒｏｘｙｃｈｌｏｒｏｑｕｉｎｅ ,Ｐｌａｑｕｅｎｉｌ)和阿的平(ｑｕｉｎａｃｒｉｎｅ ,Ａｔａｂｒｉｎｅ) ,其中羟氯喹用于 90 %病例 ,阿的平已基本淘汰〔1～ 3〕。1　药理特性〔1～ 3〕1 1　阿的平　是具有 1个外苯环的吖啶化合物。口服后迅速吸收 ,8～ 12…     

β胡萝卜素治疗红细胞生成性原卟啉病和其他光感性疾病

作者等自1970年以来,应用口服大剂量β胡萝卜素(Solatene)治疗133例红细胞生成性原卟啉病(EPP)、27例多形性日光疹(PMLE)、6例目光性荨麻疹、3例夏令疱疹、1例迟发性皮肤卟啉病及2例光化性类网状细胞增生病(actinic reticuloid),以求改善与这些疾病相关的光感性。     

多形性日光疹的细胞免疫学研究

多形性日光疹(PLE)被视为是对日光的一种异常的延迟型反应,但迄今尚无确切的基础科学证据支持这一假设.据此,作者用以下三项免疫学试验对55例PLE患者进行了研究,并与58例皮肤迟发性卟啉病(PCT,一种光毒性机制参与的疾病)患者作了比较.     

物理性皮肤病

950268 光敏性皮肤病患者血清中锌、铜、镁、铁含量测定/王侠生…//中国皮肤性病学杂志。-1994,8(3).-155～156 多形性日光疹24例,其他光敏性皮肤病11例(光化性类网织细胞增生症4例、痘疮样水疱病3例,盘状红斑狼疮2例、红细胞生成性原卟啉病及日光苔藓各1例),采用原子吸收光谱法测定其血清锌、铜、镁和铁水平,并以25例健康人为对照。结果表明活动期多形性日光疹患者血清锌、镁、铁均显著下降,其他光敏性     

中药光敏灵汤治疗光敏性皮肤病31例疗效观察

光敏性皮肤病是光线照射皮肤引起的急慢性损害如多形性日光疹、植物日光性皮炎、慢性光化性皮炎等。其发病机理复杂,表现形式多样,治法不多,效果亦不理想。笔者于1993年以来,采用中药光敏灵汤治疗,取得较满意效果。现报告如下。     

中药治疗30例光敏性皮肤病临床观察

光敏性皮肤病是一组因日光或其他光线照射皮肤引起的皮肤病，包括多形性日光疹（PMLE）、慢性光化性皮炎（CAD）等多种疾病，目前尚无满意疗法。我们采用中药凉血解毒祛风利湿法治疗该病，取得较满意疗效，现总结如下。１资料与方法１．１临床资料５２例病人均来自２００１年３月—２００１年８月我科门诊。参照文献［１］诊断标准，符合多形性日光疹（PMLE）４１例，符合慢性光化性皮炎（CAD）１１例，分成两组。治疗组３０例，男１９例，女１１例，年龄２１～５３岁，平均３６．２岁，病程２周～４年，平均３．３月，其中PMLE２４…     

慢性光化性皮炎发病机制及治疗

慢性光化性皮炎是与日光照射高度相关的慢性光敏性皮肤病,发病机制暂未完全明确,当前普遍认为与紫外线引起的迟发性超敏反应、免疫功能紊乱及炎症反应相关.治疗主要使用预防措施及局部使用糖皮质激素为主,对急性期及重型患者也可使用硫唑嘌呤、环孢素及羟氯喹等进行治疗.可通过手术治疗达到对皮肤外观有严格要求者的期望.     

仙特敏治疗多形性日光疹21例疗效观察

仙特敏治疗多形性日光疹２１例疗效观察徐义华（江苏省溧阳市皮肤病防治站２１３３００）我们用仙特敏（西替利嗪）治疗多形性日光疹２１例，并与氯喹进行临床疗效对比。现总结如下：１临床资料１．１４１例患者随机分两组，治疗组：男５例，女１６例；年龄２３至４２岁，...     

氯喹和羟基氯喹疗法在眼科方面的副作用

抗疟药对几种皮肤病和风湿病已有长久的规范的治疗形式,尤其是光敏感性疾病,如红斑狼疮和多形性日光疹(表1)。早先主要使用磷酸氯喹,继而对其药理学和毒性获得广泛的了解。近来,羟基氯喹成为较受欢迎的药。对羟基氯喹无效的病人仍使用氯喹。按特性,氯喹有许多机会导致不可逆的皮肤色素增殖,而羟基氯喹即使有的话,也是罕见的。本文综述关于这些药物对眼的毒性的已知资料,并评价对使用抗疟药病人的各种眼科检查的价值。     

氟芬那酸丁酯软膏联合糠酸莫米松乳膏治疗多形性日光疹疗效观察

目前包括多形性日光疹在内的光线性皮肤病临床常使用糖皮质激素治疗,但长期使用会出现皮肤萎缩等不良反应,且光线性皮肤病多发生在曝光部位,会加重糖皮质激素外用的不良反应。氟芬那酸丁酯是一种外用非甾体类抗炎药,研究发现,其对紫外线所致皮肤损伤有显著的治疗作用［1］。我们采用氟芬那酸丁酯软膏联合糠酸莫米松乳膏治疗多形性日光疹,取得了良好疗效,报道如下……     

Photodermatoses in Lagos

Light-sensitive dermatoses do not constitute a major problem among the black people in Nigeria. In a 10-year study, only 64 cases (about 0.4% of all dermatologic patients) had light-sensitive dermatoses. Seven of the 10 patients with endogenous photodermatoses were albinos. Two patients with polymorphic light eruption were visiting Caucasians. Only one normally pigmented black Nigerian had xeroderma pigmentosum. Fifty-four patients had photodermatoses from exogenous causes, of which hydroquinone-induced exogenous ochronosis constituted the largest group of patients. Two women had estrogen-induced porphyria cutanea tarda.     

Systemic photoprotection

At present, three classes of compounds are used as systemic photoprotective agents, but only for specific indications, not for general use in healthy individuals. Beta-carotene prevents or lessens photosensitivity in most patients with erythropoietic protoporphyria and in some patients with other photosensitivity diseases. The antimalarial drugs can clear up skin lesions in patients with polymorphous light eruption and solar urticaria who cannot obtain relief with topical sunscreens and in some patients with porphyria cutanea tarda. Oral psoralens and controlled exposure to sunlight or artificial sources of UVA radiation can increase tolerance to sunlight in fair-skinned individuals and in certain patients with vitiligo or polymorphous light eruption.     

Synthetic antimalarials

The antimalarials, mainly chloroquine and hydroxychloroquine, derive from the quinoleine core of quinine. Their initial therapeutic indication was the treatment of malaria attacks but, because of anti-inflammatory and immuno-modulatory activities, they have been since used to treat many other pathologies, in particular dermatological ones. For some of these pathologies, lupus or porphyria cutanea tarda for example, the use of these molecules is based on obvious scientific evidence. For other pathologies (cutaneous sarcoidosis, polymyositis, polymorphous light eruption...), the data on the medical literature corroborating the daily clinical practice are extremely poor. Their toxicity is limited. Their most common toxic effects are gastrointestinal (mild nausea or diarrhea) or mucocutaneous (reversible skin or mucosal pigmentation). Their most serious and dreaded side effect, retinopathy, can be largely prevented by using amounts of APS adapted to the weight of the patients. The recommended "safe" daily dose for hydroxychloroquine is 6.5 mg per kilogramme of body weight and for chloroquine 4 mg per kilogramme of body weight. However, at 6- to 12 months intervals, follow-up eye examinations should be performed.     

Repair of DNA damage in light sensitive human skin diseases

Summary Repair of UV-light induced DNA damage and changes in the semiconservative DNA synthesis were studied by in vitro autoradiography in the skin of patients with lightdermatoses (polymorphous light eruption, porphyria cutanea tarda, erythropoietic protoporphyria) and xeroderma pigmentosum as well as in that of healthy controls. In polymorphous light eruption the semiconservative DNA replication rate was more intensive in the area of the skin lesions and in the repeated phototest site, the excision repair synthesis appeared to be unaltered. In cutaneous porphyrias a decreased rate of the repair incorporation could be detected. Xeroderma pigmentosum was characterized by a strongly reduced repair synthesis.     

The quality of life of 790 patients with photodermatoses

Background  Polymorphic light eruption and erythropoietic protoporphyria (EPP) have been demonstrated to have a moderate and large impact on the quality of life (QoL) of patients, respectively. However, there is little information available about the impact of other photodermatoses on QoL.
Objectives  To assess and compare the impact of all forms of photodermatoses on patients' QoL using the standard 1-week Dermatology Life Quality Index (DLQI) questionnaire and a modified questionnaire to assess the impact over the previous year.
Methods  All patients with photodermatoses seen between 2001 and 2005 at five U.K. photobiology centres were contacted by post on the same day during a forecasted sunny week across the U.K. and asked to complete DLQI questionnaires.
Results  A total of 1877 patients were contacted. Seven hundred and ninety-seven (42%) patients replied, with a range from 30% to 48% for the five individual centres. Nearly two-thirds of patients with actinic prurigo (AP) and more than one-third of patients with photoaggravated dermatoses (PAD), chronic actinic dermatitis, EPP and solar urticaria had a DLQI of > 10, confirming a very large effect of the disorders on QoL. Of the cutaneous porphyrias, both variegate porphyria (median DLQI 3) and porphyria cutanea tarda (median DLQI 1·5) had a much lower impact on QoL than EPP.
Conclusion  This is the first large-scale study to attempt to measure the impact of a range of photodermatoses on QoL. Photodermatoses have a major impact on QoL. This impact is highest in AP and PAD.     

Naproxen-induced pseudoporphyria presenting a diagnostic dilemma

A case of clinical porphyria cutanea tarda posed a diagnostic dilemma when screening tests for porphyrinuria gave negative results and two skin biopsy specimens failed to show the histologic picture of porphyria cutanea tarda, pseudoporphyria, or epidermolysis bullosa acquisita. The dilemma was resolved when the eruption cleared following elimination of naproxen from the patient's treatment. Subsequent naproxen challenge resulted in new bullae on the dorsum of the hands.     

Die wirkung einiger lösungsmittel auf die epidermis

Summary The pathogenetic role of liver damage in photodermatoses induced by oral contraceptives was investigated. From among 121 cases with photodermatosis, it was in 4 cases of polymorphic light eruption-like dermatosis and in 2 cases of porphyria cutanea tarda that a longterm use of antibaby pills preceded the development of skin disease. Physical and biochemical studies of the liver of the patients suggested that the hepatotoxicity of the estrogen component of oral contraceptives can play a role not only in the pathomechanism of porphyric cases, but also in that of cases occurring with the clinical picture of polymorphic light eruption.

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Zusammenfassung Die pathogenetische Rolle der Leberschädigung wurde in Fällen von durch orale Kontrazeptiva induzierten Lichtdermatosen untersucht.In einem Krankengut von 121 Lichtdermatosen ging eine langfristige Einnahme der oralen Kontrazeptiva der Manifestation der Hautkrankheit in 4 Fällen von chronisch-polymorphen Lichtausschlägen und in 2 Fällen von Porphyria cutanea tarda voraus. Die Ergebnisse der biochemischen Untersuchungen der Leberfunktion wiesen darauf hin, daß die Hepatotoxicität der Oestrogenkomponente der oralen Kontrazeptiva nicht nur im Pathomechanismus der Porphyria cutanea tarda, sondern auch im Pathomechanismus von denen, die im klinischen Bilde der chronisch-polymorphen Lichtausschläge erscheinen, eine Rolle spielen kann.

     

The sensitivity and specificity of "caterpillar bodies" in the differential diagnosis of subepidermal blistering disorders

Caterpillar bodies are eosinophilic, elongated, segmented bodies located within the roofs of blisters and are considered to represent a specific histopathologic feature of porphyric bullous eruptions, including porphyria cutanea tarda and erythropoietic protoporphyria. The possibility that similar or identical bodies may be present in other disorders prompted further study exploring the specificity of caterpillar bodies in the differential diagnosis of subepidermal vesiculobullous disorders. Seventy-six cases exhibiting subepidermal clefting were reviewed by light microscopy. "Classic" caterpillar bodies were present in porphyria cutanea tarda (6 of 14) and 1 case representing either venous stasis-associated bulla or possibly bullosis diabeticorum. Caterpillar body-like clusters were present in porphyria cutanea tarda (5 of 14), erythropoietic protoporphyria (1 of 3), bullous pemphigoid (7 of 24), and junctional or dystrophic epidermolysis bullosa (3 of 5). In some cases, classic caterpillar body and caterpillar body-like clusters coexisted in a blister roof. Caterpillar bodies or caterpillar body-like clusters were not identified in any cases of dermatitis herpetiformis, linear IgA bullous dermatosis, bullous erythema multiforme, epidermolysis bullosa acquisita, or wound-healing reactions. In contrast to caterpillar bodies, caterpillar body-like clusters were negative for PAS or Type IV collagen stains. In conclusion, caterpillar bodies appear to represent a specific feature of porphyria cutanea tarda (specificity, 98%) but were present in less than half of those cases in this study (sensitivity, 43%). Caterpillar body-like clusters are less specific and may be present in porphyria cutanea tarda, erythropoietic protoporphyria, pseudoporphyria, bullous pemphigoid, epidermolysis bullosa, and epidermolysis bullosa acquisita.     

Hypertrichosis as the presenting feature of porphyria cutanea tarda

We report a case of porphyria cutanea tarda in which the only cutaneous abnormality and initial presenting complaint was hypertrichosis. The patient had a history of excessive alcohol consumption. Alcohol avoidance and treatment with low-dose hydroxychloroquine resulted in resolution of the hypertrichosis and normalization of biochemical abnormalities.     

Co-inheritance of mutations in the uroporphyrinogen decarboxylase and hemochromatosis genes accelerates the onset of porphyria cutanea tarda

Porphyria cutanea tarda is a skin disease caused by photosensitization by porphyrins whose accumulation is caused by deficiency of hepatic uroporphyrin- ogen decarboxylase activity. Mutations in the uroporphyrinogen decarboxylase gene are present in the low-penetrant, autosomal dominant familial form but not in the commoner sporadic form of porphyria cutanea tarda. We have investigated the relationship between age of onset of skin lesions and mutations (C282Y, H63D) in the hemochromatosis gene in familial (19 patients) and sporadic porphyria cutanea tarda (65 patients). Familial porphyria cutanea tarda was identified by mutational analysis of the uroporphyrinogen decarboxylase gene. Five previously described and eight novel mutations (A80S, R144P, L216Q, E218K, L282R, G303S, 402-403delGT, IVS2 + 2 delTAA) were identified. Homozygosity for the C282Y hemochromatosis mutation was associated with an earlier onset of skin lesions in both familial and sporadic porphyria cutanea tarda, the effect being more marked in familial porphyria cutanea tarda where anticipation was demonstrated in family studies. Analysis of the frequencies of hemochromatosis genotypes in each type of porphyria cutanea tarda indicated that C282Y homozygosity is an important susceptibility factor in both types but suggested that heterozygosity for this mutation has much less effect on the development of the disease.