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文章来源：皮科周讯
结核病是人类已知的最古老的疾病之一，目前仍威胁着全球，据报道，每年有800-900万新的活动性疾病。结核病是大多数人类免疫缺陷病毒（HIV）合并感染患者的最终死亡的主要原因。皮肤结核（CTB）并不常见，占所有肺外结核病表现的1-1.5%，肺外结核仅占所有结核病病例的8.4-13.7％。
CTB更精确的分类包括接种性结核、内源性结核和血源性结核。此外，明确区分由结核分枝杆菌引起的典型CTB和由非典型分枝杆菌引起的CTB。由分枝杆菌引发的皮损可从小丘疹（例如原发接种性结核）和疣状皮损（例如疣状皮肤结核）发展为大面积溃疡（例如Buruli溃疡）和斑块（例如寻常狼疮），引发严重畸形。
目前CTB治疗方案局限于常规口服疗法和偶尔的手术干预治疗（有需要时）。典型CTB采用利福平、乙胺丁醇、吡嗪酰胺、异烟肼和链霉素（根据个体需要）联合治疗。非典型分枝杆菌感染对多数抗结核药物耐药，并只对某些抗生素反应。肺结核病例中，尽管患者依从性差，但是有各种相对广泛的治疗方案可供选择。多药耐药和极度耐药菌株的发展影响其治疗效果。迄今为止，尚未有局部治疗CTB的疗法 ，虽然常规疗法大多数呈现积极疗效，但缺乏其他治疗方案。
结核病（TB）是人类最古老的疾病之一。地球既是人类居住地，也是该疾病蔓延地。在埃及木乃伊中已发现典型结核病损害，含抗酸杆菌（AFB）。十七和十八世纪，结核病发病率急剧增加，之后200年发病率下降。尽管卫生改善和免疫疗法使疾病再次降低，但十九世纪后期，结核病再度成为主要的健康问题。
现在，TB仍显著的威胁着公共健康。世界卫生组织（WHO）估计，全球约20-40%人口受到影响，据报道，每年新增800万-900万活动性疾病病例。结核病是大多数感染人类免疫缺陷病毒（HIV）患者最终死亡的主要原因。
尽管TB是一种广泛传播的疾病，特别在发展中国家，8.4-13.7％病例表现为一种肺外疾病。数据差异和较低值表明该疾病的罕见性和不确定性。这增加了HIV合并感染的可能性。皮肤结核（CTB）比较少见，并不是一个明确疾病，仅占所有肺外表现的1-1.5％。Theophile Laennec（听诊器的发明者），1826年描述了第一例CTB病例。CTB在女性中盛行，最常见于青少年。CTB最常累及面部，尽管其也常见于颈部和躯干。
CTB有许多不同表现，诊断比较复杂。耐多药结核病的增加也导致CTB发生增加。由结核分枝杆菌引起的皮肤感染表现称为典型CTB，但一些其他分枝杆菌也引发皮肤表现，如表1所示。分枝杆菌可被细分为两个亚属，即迅速/快速生长型和慢速生长型。生长缓慢病原体培养期超过7天，逐渐成熟，而快速生长病原体培养期小于等于7天。
表1 非典型分枝杆菌引发的皮肤感染。
过去，由于对CTB缺乏准确分类，导致对相关疾病存在许多疑惑。近年来，根据3个标准，即发病机制、临床表现和组织学评估，确定了更精确的分类系统。根据这些标准，CTB可被分为：
外源接种性结核病。
内源性结核病。
血源性结核病。
下面将描述这些标准和症状。
外源接种性结核病
原发接种性结核（图1），又称结核下疳，由分枝杆菌通过未感染结核分枝杆菌患者或对结核分枝杆菌无免疫力患者的破损皮肤侵入皮肤或粘膜引发。分枝杆菌可通过消毒不充分的针头、纹身、包皮环割切术、穿孔、手术、创伤和口对口复苏术穿过皮肤屏障。据报道，皮损常呈孢子丝菌样。可以通过各种方式接种，且医疗行业工作人员被感染风险最高。1826年Theophile Laennec发现了剖尸疣，这实际上记录了首例CTB案件如何被描述。皮肤黏膜对CTB的感染作用，约占总报告病例的三分之一。包括通过口腔（拔牙后）或结膜感染。
外源性接种可引发已感染结核病患者和中度至高度免疫患者手指或其它四肢出现疣状皮损，称为疣状皮肤结核（TVC）。TVC（也称剖尸疣、疣状狼疮和疣状结核）开始为疼痛、小丘疹周围环绕紫色、炎性光晕，后发展为无症状疣状皮损，如图2所示。TVC占4.4-16%，见于年轻患者。
内源性结核病
CTB也可由皮下上方皮肤感染或破损引发，常由淋巴结（淋巴结核），或骨结核和关节结核继发而来，之前称为瘰疬性皮肤结核（图3和图4）。皮损初起为皮下可移动结节，随后很快与其表面皮肤粘连。然后破溃，最终形成皮肤脓肿。这些脓肿可自行愈合，但需要数年才能彻底治愈。瘰疬性皮肤结核是十岁以下儿童最常见的CTB，发病率为36-48％。瘰疬性皮肤结核病例示，35％患者可有全身性结核感染，特别是肺结核。这些皮损更多见于腋下、颈部、腹股沟和胸部。
腔口结核（图5）是罕见的CTB，活的病菌被咳出或在免疫力低下患者中传播，在黏膜处自发接种引发。具有正常抵抗力的组织被侵袭，通位于常鼻、口腔、会阴部和/或直肠周围部位。损伤处疼痛和溃烂，不会自然愈合。受感染患者可发展为渐进性肺、外阴、泌尿或肠结核。据报道，在一些中国病例中，腔口结核和瘰疬性皮肤结核可见干酪样坏死。
血源性结核
大多数CTB病例为血源性传播或淋巴播种。当AFB从感染原始部位扩展到身体其他部位，就会产生血源性结核。此外，其包括对结核病高度过敏的已过敏患者发展为慢性CTB。最常见的感染形式为寻常狼疮，其最有可能导致容貌损毁。
结核性树胶肿（图6）是罕见的血源性结核病，发病率仅为1-2％。皮损开始为坚硬结节，随后溃破形成脓肿，最终形成溃疡。结节和广泛性干酪样坏死通常可辨别。这些溃疡AFB通常呈阴性。
寻常狼疮（LV）（图7）继发于卡介苗(BCG)接种后或原发接种性结核，或由接种导致。LV在年幼儿童中很常见，儿童和青少年发病率为41-68%。LV主要有五种形式，其中斑块形式最常见，约占所有病例的32％。LV的斑状形式开始为扁平、红棕色丘疹，逐渐发展为浅肤色斑块。其可出现不规则性瘢痕和斑块边缘通常增厚和角化过度。
Summary
Tuberculosis is one of the oldest diseases known to humankind and it is currently a worldwide threat with 8-9 million new active disease being reported every year. Among patients with co-infection of the human immunodeficiency virus (HIV), tuberculosis is ultimately responsible for the most deaths. Cutaneous tuberculosis (CTB) is uncommon, comprising 1-1.5% of all extra-pulmonary tuberculosis manifestations, which manifests only in 8.4-13.7% of all tuberculosis cases.
A more accurate classification of CTB includes inoculation tuberculosis, tuberculosis from an endogenous source and haematogenous tuberculosis. There is furthermore a definite distinction between true CTB caused by Mycobacterium tuberculosis and CTB caused by atypical mycobacterium species. The lesions caused by mycobacterium species vary from small papules (e.g. primary inoculation tuberculosis) and warty lesions (e.g. tuberculosis verrucosa cutis) to massive ulcers (e.g. Buruli ulcer) and plaques (e.g. lupus vulgaris) that can be highly deformative.
Treatment options for CTB are currently limited to conventional oral therapy and occasional surgical intervention in cases that require it. True CTB is treated with a combination of rifampicin, ethambutol, pyrazinamide, isoniazid and streptomycin that is tailored to individual needs. Atypical mycobacterium infections are mostly resistant to anti-tuberculous drugs and only respond to certain antibiotics. As in the case of pulmonary TB, various and relatively wide-ranging treatment regimens are available, although patient compliance is poor. The development of multi-drug and extremely drug-resistant strains has also threatened treatment outcomes. To date, no topical therapy for CTB has been identified and although conventional therapy has mostly shown positive results, there is a lack of other treatment regimens.
Introduction
Tuberculosis (TB) is one the oldest diseases of humankind. As humanity populated the earth, so did this disease spread as well. Typical tuberculous lesions, containing acid-fast bacilli (AFB), have been identified in Egyptian mummies. The prevalence of TB increased dramatically during the seventeenth and eighteenth centuries, after which it declined over the next two-hundred years . Later in the nineteenth century, TB again became a major health concern, although improved hygiene and immunisation caused the disease to wane again.
TB today continues to pose a significant public health threat. The World Health Organization (WHO) estimates that approximately 20-40% of the world's population are affected, with 8-9 million new cases of active disease being reported every year. TB is ultimately responsible for most deaths among patients infected with the human immunodeficiency virus (HIV).
Despite TB being such a widespread disease, especially in developing countries, it manifests only as an extra-pulmonary disease in 8.4-13.7% of cases. The difference in data and the low values may also indicate how uncommon and undefined this disease truly is. This increases with co-infection of HIV. Cutaneous tuberculosis (CTB) is relatively uncommon and not a well defined disease, comprising only 1-1.5% of all extra-pulmonary manifestations. Theophile Laennec, inventor of the stethoscope, described the first example of CTB in 1826. CTB is prevalent among women, mostly young adults. The most common site of CTB infection is the face, although it often appears on the neck and torso as well.
CTB has many different manifestations, which complicates diagnosis. The increase in multi-drug resistant TB has also resulted in an increase in the occurrence of CTB. Skin manifestations of infections caused by Mycobacterium tuberculosis are known as true CTB, but some of the other species of the Mycobacterium genus are also responsible for cutaneous manifestations, as summarised in Table 1. Mycobacteria can be sub-divided into two sub-genera, namely rapid/fast growers and slow growers. Slow growing organisms have a more than 7 days incubation period for mature growth, whereas rapidly growing organisms have a 7 days or less incubation period for mature growth.
Table 1 Atypical mycobacterium species responsible for cutaneous infections.
To date, no topical therapy exists for any of the TB infections. Although most of the current treatment regimens have demonstrated positive results, they are not all completely effective, especially with the rise in multi-drug and extremely drug-resistant TB strains. The potential of using topical treatments to aid in treating TB thus need to be evaluated for improving therapeutic regimens.
Classification of cutaneous tuberculosis
In the past, the lack of an accurate classification of CTB has accounted for much of the confusion relating to the disease. In recent years, a more accurate classification system has been developed, using three criteria, i.e. pathogenesis, clinical presentation, and histologic evaluation. Using these criteria, CTB can be classified as:
Inoculation tuberculosis from an exogenous source.
Tuberculosis from an endogenous source.
Haematogenous tuberculosis.
These criteria and their symptoms are described next.
Inoculation of tuberculosis from an exogenous source
Primary inoculation TB (Figure 1), also known as tuberculous chancre, results from the entry of mycobacteria into the skin, or mucosa, through broken skin of a person not previously being infected with, or who has no immunity against Mycobacterium tuberculosis. The access of mycobacteria through the skin barrier can be caused by inadequately sterilised needles, tattooing, circumcision, piercings, operations, wounds and post mouth-to-mouth resuscitation. The lesions have often been reported as having a sporotrichoid appearance. Inoculation can occur through various methods and persons working in a medical profession are most at risk of being infected. This was in fact how the first case of CTB was described by Theophile Laennec in 1826, when he noted his own “prosector's wart”. Mucocutaneous contribution towards CTB accounts for approximately one-third of the total number of reported cases. These include infection through the oral cavity (after tooth extraction), or of the conjunctiva.
Figure 1. Inoculation tuberculosis in a child
Exogenous inoculation can cause a warty lesion on the fingers, or other extremities, called tuberculosis verrucosa cutis (TVC), in patients previously infected with TB and who have moderate to high immunity. TVC (also known as prosector's wart, lupus verricosus and warty tuberculosis) starts as a painful, small papule, surrounded by a purple, inflammatory corona that progresses into an asymptomatic warty lesion, as illustrated in Figure 2. TVC may, in 4.4-16% of cases, present in younger patients.
Figure 2. Tuberculosis verrucosa cutis
Tuberculosis from an endogenous source
CTB may also result from the involvement and breakdown of the skin covering a subcutaneous focus, usually a lymph gland (tuberculous lymphadenitis), or TB of the bones and joints, previously described as scrofuloderma (Figures 3 and 4). The lesions start as a subcutaneous, mobile nodule, which soon after attaches to the overlying skin. A discharge then starts and eventually a cutaneous abscess forms. These abscesses may heal spontaneously, although it takes years to completely cure. Scrofuloderma is the most common form of CTB among children younger than ten years of age, with a prevalence of 36-48% . Scrofuloderma suggests that the patient may have a systemic TB infection, particularly pulmonary TB, in 35% of cases. These lesions are more often seen in the axillae, neck, groin and chest.
Figure 3. Scrofuloderma
Figure 4. Scrofuloderma in a male patient showing lymph gland involvement.
Orifacial TB (Figure 5) is a rare form of CTB and results from the auto-inoculation of the mucous membrane that occurs when viable organisms are either expectorated, or spread in patients with low immunity. Tissue, normally resistant to infection, is invaded, usually in the nose, oral cavity, perineal and/or perirectal areas. Such esions are painful and ulcerative and do not heal naturally. Patients with these infections are likely to have progressive pulmonary, genital, urinary or intestinal TB. In some cases in China, caseation necrosis, visible in orifacial TB and scrofuloderma, has been reported.
Figure 5. Orifacial tuberculosis.
Haematogenous tuberculosis
Haematogenous spread or lymphatic seeding, accounts for the majority of CTB cases. Haematogenous TB occurs when the AFB spread from a primary site of infection to the rest of the body. Also, it involves chronic CTB in a previously sensitised patient with a high level of TB sensitivity. The most common form of this infection is lupus vulgaris, which also has the highest potential for disfigurement.
Tuberculous gamma (Figure 6) is a rare form of haematogenous tuberculosis, with an incidence of only 1-2%. The lesions start as firm nodules, which later break down to form abscesses and ultimately ulcers. Tubercles and widespread caseation necrosis are often identifiable. These ulcers are frequently negative for AFB.
Figure 6. Tuberculous gamma on the dorsum of the right foot of an eight-year old boy.
Lupus vulgaris (LV) (Figure 7) may develop after Bacille Calmette Guerin (BCG) vaccination, or from primary inoculation TB, or as a result of inoculation. LV is also very common among younger children, with a prevalence of 41-68% in affected children and adolescents. LV may present in mainly five general forms, of which the plaque form is the most common, representing approximately 32% of all cases. This form of LV starts as a flat, red-brown papule, which slowly expands into a light skin-coloured plaque. It may show irregular areas of scarring and the edge of the plaque is often thickened and hyperkeratotic.
Figure 7. Lupus vulgaris plaque of the face, neck and chest.
由MediCool医库软件王盼 编译，上海市皮肤病医院陈裕充博士审核
原文来自：Tuberculosis 95 (2015) 629e638
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