麻风的诊断与治疗

麻风的诊断与治疗,概念,麻风（leprosy）又称Hansen病。由麻风分枝杆菌（Mycobacterium leprae）引起的一种慢性传染性疾病，主要侵犯皮肤、黏膜和周围神经，少数情况下可侵犯深部组织和内脏器官。,Dr. GH Armauer Hansen( Norway) and his Patient,The Louisiana Leper Home was established in 1894 to provide a place of refuge, not reproach; a place of treatment and research, not detention.,流行病学,流行区域：世界性：非洲、东南亚、拉丁美洲和西太平洋地区中国：沿海与长江流域发病情况：青壮年男女之比3:1家庭聚集性社会因素影响：贫穷、居住环境、伴有HIV感染等,流行病学,传染源：人是唯一传染源，特别是未经治疗的多菌型麻风病人是主要传染源传播途径：传统观点：与麻风病人长期接触新近观点：与肺结核类似的空气传播易感人群：取决于人体的免疫反应与功能正常成人一般感染后不发病,Leprosy is asymmetrically distributed globally, with the greatest incidence and prevalence in the developing world. Globally, the incidence has fallen by 70% and the prevalence has fallen by 90% since 2000 thanks to aggressive eradication efforts with multidrug treatment regimens.,病因与发病机制,麻风杆菌（Mycobacterium leprae）革兰染色阳性，抗酸染色阳性形态多样，与病人治疗情况密切相关迄今体外培养未成功,病因与发病机制,发病机制主要分布于皮肤（主要位于真皮层的末梢神经、巨噬细胞、立毛肌、毛囊与皮脂腺）、黏膜（主要是鼻黏膜）、周围神经（不侵入中枢神经），引起相应病理反应。破损皮肤和鼻黏膜排出大量麻风杆菌，为麻风主要传染源。,Mycobacterium leprae is an acid-fast, rod-shaped bacillus. It is an obligate, intracellular organism that preferentially proliferates in tissues with cooler temperatures. The organism exhibits the longest reproduction time among all bacteria, requiring 13 days to double in experimentally infected mice, and with an incubation time of up to 50 years in humans.,In the United States, armadillos(南美犰狳) are a major reservoir of leprosy infection. They are one of the few animals known to become infected and are used in research efforts to study the disease. They have an unusually low body temperature of around 34C, which is hospitable to M leprae growth.,临床表现,平均潜伏期25年。发病率约15%。因患者免疫力不同，临床表现差异较大，几乎涉及临床各个学科。,临床表现,皮肤表现：皮损形态多样：有斑疹、丘疹、结节、斑块、浸润、水疱、溃疡等皮肤附属器侵犯：表现为头发、眉毛脱落，闭汗、皮肤干燥,临床表现,与其他皮肤病不同在于：局部感觉障碍出汗障碍可找到麻风杆菌,Leprosy: tuberculoid type Well-defined, hypopigmented, slightly scaling, anesthetic macules and plaques on the posterior trunk.,Leprosy: borderline-type A 31-year old Vietnamese female. A. Geographic shaped plaque on the buttock with raised red indurated margins and central clearing. There is extension of the infection indicated by the erythematous papules beyond the margins. B. Similar geographic plaque on the legs with raised red margins and central clearing.,A,B,Leprosy: borderline-type A 26-year-old Vietnamese male. A. Well-demarcated, infiltrated,erythematous plaques on the face. B. Identical red plaques on the lower back.,A solitary, anesthetic, and annular lesion of polar tuberculoid leprosy, which had been present for 3 months. Its sharp margins, erythema, and scale are more evident than its elevation.,One of several lesions of borderline tuberculoid leprosy, which had an incompletely annular configuration with satellite papules. Compared to the polar tuberculoid lesion, there is less erythema, no evident scales, but sharp margination.,Characteristic borderline or dimorphic lesion is an indurated and elevated annular plaque,It has a well-defined “tuberculoid” interior margin but a poorly defined “lepromatous” exterior margin. Having both morphologies, it is termed “dimorphic.”,Multiple lesions in a patient with borderline lepromatous leprosy. The annular lesions vary in size and are asymmetrically distributed. In contrast, the poorly defined papular and nodular lesions are roughly symmetric. Impairment of sensation was present in most lesions.,Multiple dermatofibroma-like (histoid) lesions, which are solitary and confluent, in a patient with subpolar lepromatous leprosy. Their uniformly sharp margins and erythema are in contrast to most of the lesions in borderline lepromatous leprosy.,These multiple, barely palpable, erythematous, and asymptomatic lesions had been erupting over the previous 2 months in the same patient. With treatment, as lesions remitted, they became mildly hyperpigmented.,临床表现,周围神经症状：发生于几乎所有患者，表现为神经粗大侵犯神经：尺神经、耳大神经、正中神经、腓总神经、眶上神经、面神经、桡神经、胫神经,临床表现,周围神经症状：功能障碍：浅感觉障碍：最早最常见，温觉最早，痛觉次之，触觉最后运动障碍：肌肉萎缩或瘫痪所致，表现为爪形手、足下垂、面瘫等营养性障碍：皮肤干燥、萎缩、脱毛，易形成水疱或溃疡循环障碍：手足发绀、温度降低、肿胀出汗障碍：,The facial nerve is another commonly damaged nerve in leprosy. The patient shown has both a facial nerve palsy and contractures of the hand from leprosy.,Long-standing neuropathy in the feet can lead to nonhealing ulcers, abscess formation, and osteomyelitis. If untreated early in the disease course, deformities may occur. The image shown is of an individual with advanced lepromatous leprosy with amputation of the toes and trophic ulceration.,Plain film x-rays can demonstrate significant bony changes in patients with long-standing disease. The x-ray of the foot shows absence of the second to fifth toes and distal tapering of the metatarsals secondary to neuropathy. The phalanges of the great toe show destruction secondary to osteomyelitis.,临床表现,眼部症状：由于麻风反应、麻风本身、三叉神经受累所致，表现为慢性结膜炎、角膜炎、巩膜炎、泪囊炎、虹膜睫状体炎等。鼻部症状：鼻黏膜充血、肿胀、糜烂、结痂、结节、浸润、肥厚等。其他：咽喉不适，淋巴结肿大、骨骼和内脏受累。,麻风反应,为机体免疫系统对感染的免疫学反应发生变化所致，常导致神经损伤，但并不意味着疾病进展或治疗失败。型麻风反应： 与细胞免疫有关，又称迟发型超敏反应。免疫力增强时为升级反应或逆向反应，多发生于正规药物治疗患者，表现为界限类麻风向结核型转化，原有皮损加重或出现新发皮损。因神经反应可诱发或加重畸形。免疫力降低时为降级反应，病情加重，向瘤型方向转化。,麻风反应,型麻风反应：与体液免疫有关，又称血管炎性或免疫复合物性变态反应、麻风结节性红斑。 全身中毒症状：发热，畏寒，头痛，乏力，纳差。皮肤表现：结节性红斑，多形红斑，坏死性红斑。神经肿大、压痛其他：急性虹膜睫状体炎，睾丸炎，淋巴结肿大，白细胞升高，血沉快，尿蛋白等。,The tumidity, purplish hues, and sharp margination strongly suggest a reversal reaction. The lesions were neither painful nor tender.,Some of the initial presenting lesions in a patient with a delayed-type hypersensitivity reaction who had borderline lepromatous leprosy.,The erythema nodosum leprosum reaction is characterized by acute peripheral nerve damage and may be found in varying degrees in all forms of leprosy. Involved nerves become tender and increase in size. Claw hand (shown) and foot drop are particularly common because of involvement of the ulnar, median, and lateral popliteal nerves.,The patient shown has an erythema nodosum leprosum type 2 reaction, which occurred several weeks after initiation of drug therapy.,Two different host reaction patterns in lepromatous leprosy disease in two ears,In the ear on the left, the diffuse infiltration has become so extensive that the skin of the ear has been thrown into folds, but with no nodule formation.,On the helix of the ear on the right are four nodular lepromatous leprosy lesions, arranged chronologically, with the most recent one on top, and the oldest near the bottom.,Lesions of erythema nodosum leprosum in a patient with lepromatous leprosy. The bright-pink color is characteristic. These lesions are edematous, and pustule formation is suggested. The lesions are painful and tender.,Leprosy: lepromatous type A 60-year-old Vietnamese female with treated advanced disease. Ulnar palsy, loss of digits on right hand, and saddle-nose deformity associated with loss of nasal cartilage are seen.,Squamous cell carcinoma (carcinoma cuniculatum) in a patient with peripheral neuropathy due to leprosy A large fungating,partially necrotic and hyperkeratotic tumor on the sole of the foot. The lesion had been considered a neuropathic ulcer, ascribed to leprosy, but continued growing and became elevated and ulcerated.,辅助检查,细菌学检查：意义：诊断、分型、疗效观察、监测复发。取材方法：常规查菌部位46处（眶上、耳垂、下颌、活动性皮损）或鼻黏膜（疑为瘤型者），切刮法取材。结果判断：抗酸染色后镜检，以单位视野内细菌密度计数，结果以-6+表示，并观察细菌形态。,辅助检查,麻风菌素试验：意义：观察机体对麻风杆菌的免疫力。方法：皮内注射麻风菌素，分别于48h和3周后观察局部反应。结果判断：早期反应：根据红斑有无和浸润大小来判定，以阴性强阳性来表示。晚期反应：根据浸润性结节大小和有无溃破来判定，以阴性强阳性来表示。,辅助检查,其他检查：未列入临床常规检查，有条件实验室的流行病学检查血清学检查：检查血清抗体，如荧光麻风抗体血清试验（FLA-ABS）、ELISA、RIA分子生物学检查：检测DNA片段，如PCR,组织病理检查,取材于活动性皮损，如红斑、结节、浸润性皮损等。HE染色：不同类型具有不同病理学特征。抗酸染色：查找麻风杆菌。,Tuberculoid leprosy: Elongated epithelioid granuloma without caseation necrosis around neurovascular bundles. (Low power),Lepromatous leprosy: Nodular granulomatous infiltrate with grenz zone. (Scanning power),Lepromatous leprosy: Nodular granulomatous infiltrate with grenz zone. (Low power),Lepromatous leprosy: Nodular granulomatous infiltrate. Numerous bacilli within histiocytes on Fite stain. (High power),Erythema nodosum leprosum: Fibrinoid necrosis of the congested vessel. (High power,诊断,诊断标准：需特别慎重，强调早期诊断和准确诊断，细菌学检查为金标准。具有下列4条中2条或以上，或符合第3条，即可确诊。有皮损，并伴浅感觉障碍及闭汗，或有一片麻木区；周围神经干或皮支神经粗大；皮损或组织切片查到麻风杆菌；病理组织中见到特异性病变。,诊断,分型：5级分类法：TT、LL、BB、BT、BL，早期为IL，各型根据免疫强度可相互转化。麻风杆菌数量： LL BL BB BT TT细胞免疫反应强度： TT BT BB BL LL根据皮肤涂片查菌结果，可分为多菌型（MB）和少菌型（PB），用以指导化疗。,鉴别诊断,与其他皮肤病鉴别：极多，主要包括结节病、环状肉芽肿、寻常狼疮、结节性红斑等。主要区别在于：皮损感觉，或有无伴发麻木和出汗；有无浅神经粗大；麻风杆菌检查。,鉴别诊断,与神经系统疾病鉴别：主要包括股外侧皮神经炎、非麻风性周围神经炎、进行性增殖性间质性神经炎。主要区别在于：伴有皮损；以浅神经粗大为主。,1.单纯糠疹：儿童青少年好发，面颈躯干部鳞屑性淡色斑，无自觉症状，有时瘙痒2.继发性色素减退：花斑癣，银屑病，玫瑰糠疹痊愈后；,3花斑癣:俗称汗斑,为真菌感染,浅色斑疹,出汗后有轻度瘙痒.,4.贫血痣：发生于躯干，生后就有局限性色素减退斑，持续终生，随年龄可扩大。,5.玫瑰糠疹：好发躯干，四肢近心端，椭圆形淡红斑，中心略黄色，边缘有薄屑，皮损与皮纹一致，春秋好发。病前1-2周有病毒感染史。轻痒或几无症状。,6.斑块型银屑病：属于寻常型，见于静止期。为躯干四肢搞出皮面斑块，表面有鳞屑，头部也常有皮损，有痒感。,7.体癣,股癣：丘疹水疱组成的环状损害，有瘙痒，中心消退，进展快，真菌检查阳性。,8.脂溢性皮炎：头、眉、鼻、耳后、颈、前胸、上背肩胛部皮脂腺丰富部黄红色斑、斑丘疹，表面有油腻性鳞屑，干性红斑上有白色糠秕样鳞屑。不同程度瘙痒。,9.蕈样肉芽肿：皮肤T细胞淋巴瘤。病程慢性，红斑期常见红色或红褐色斑片，椭圆形，有鳞屑，多见躯干，瘙痒，持续多年。斑块期为浸润斑块，结节，光亮，红色，黄红色，或褐色。肿瘤期隆起斑块结节，半球或分叶状，可破溃。主要根据病理确诊，表皮内有Pautrier小脓肿，肾形核深染细胞核。,9.蕈样肉芽肿：,9.蕈样肉芽肿：,10. 结节性红斑：中青年女性多见，春秋好发，急性发病，双下肢好发，为皮肤鲜红斑 ，皮下蚕豆大小结节，压痛，病前有上呼吸道感染史。,11.离心性环状红斑：昆虫、真菌，内脏肿瘤引起的反应性病变。初单个水肿性丘疹，渐向周围扩大，中心痊愈，呈环状，边缘可有鳞屑，好发四肢躯干。轻度瘙痒。,12.环状肉芽肿：初为丘疹或结节，渐成环状皮损，隆起皮面，有斑块型损害。多见手背、足、小腿。病程慢性，2年左右自然消退。,12.环状肉芽肿：,13.结节病：有丘疹、结节、斑块，好发面、颈、肩、臀部。初为丘疹结节，红色或紫红，后成斑块，中心消散凹陷，边缘隆起成环状。多见30-50岁成年人。,17.二期梅毒疹：感染后7-10周或硬下疳后6-8周发病。有斑疹、斑丘疹，鳞屑性皮疹，不痒，泛发全身，对称分布。有粘膜斑，扁平湿疣，暗视野螺旋体阳性，梅毒血清学阳性。,18.亚急性皮肤红斑狼疮：中青年女性为主。皮损初为红色水肿性丘疹，渐成环形或多环形，边缘隆起，有细小鳞屑，不痒。皮损中央消退后，有浅灰色色素沉着和毛细血管扩张。另有一型为丘疹鳞屑型，皮损类似银屑病。有光敏，脱发，雷诺现象、甲周毛细血管扩张等。ANA+，Ro+，La+，dsDNA+，Sm+，直接免疫荧光检查见皮损表皮真皮交界处IgG沉积,19.持久性隆起红斑：肢体关节