ReviewCutaneous tuberculosis overview and current 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 [1], [2], [3], [4]. The prevalence of TB increased dramatically during the seventeenth and eighteenth centuries, after which it declined over the next two-hundred years [5]. Later in the nineteenth century, TB again became a major health concern, although improved hygiene and immunisation caused the disease to wane again [6], [7], [8].
TB today continues to pose a significant public health threat. The World Health Organisation (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 [9], [10], [11], [12], [13], [14], [15], [16]. TB is ultimately responsible for most deaths among patients infected with the human immunodeficiency virus (HIV) [17], [18], [8], [19], [20].
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 [21], [22], [23], [24], [25], [12], [26], [8], [27], [28], [29], [20], [30]. Théophile Laennec [8], 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 [31].
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 [32], [33], [8], [34], [35].
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.
Section snippets
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 [2], [22], [37], [38], [7], [39], [40], [41], [42], [43], [29]. Using these criteria, CTB can be classified as:
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Inoculation tuberculosis from an exogenous source.
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Tuberculosis from an endogenous source.
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Atypical mycobacterium infections of the skin
More than 135 species of atypical Mycobacterium [or more recently known as non-tuberculous mycobacteria (NTM)] have been described [32], [80], [81], [34], but only a few show cutaneous manifestations, as summarised in Table 1, of which only the most common ones are discussed in this article, namely:
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Mycobacterium marinum.
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Mycobacterium ulcerans, or Buruli ulcer.
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Mycobacterium haemophilum.
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Mycobacterium fortuitum.
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Mycobacterium chelonae.
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Mycobacterium abscessus.
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Mycobacterium leprae, or Hansen's
Current treatment regimens of cutaneous tuberculosis
Most cutaneous tuberculosis forms are sensitive to anti-tuberculous therapy taken orally [54], [25], [99], [55], [44], [40], [34], [60]. Mycobacterium tuberculosis has the ability to create drug resistance and to avoid this, several anti-tuberculous drugs are administered simultaneously. Frequent treatment is required (daily or every 3 days, according to individual need) in a combination of drugs and for a sufficiently long duration to ensure that the lesions are completely free of infection.
Summary
TB poses a major health challenge worldwide [104], [50], [41], [105]. CTB is an uncommon form of TB, with only a 1–1.5% prevalence among all reported extra-pulmonary TB cases [21], [27], [29], [20], [30]. CTB is difficult to diagnose, due to its rare nature and the fact that it may present in various clinical forms [55], [110], [65]. Such clinical presentations can vary from small papules, warty lesions, ulcers, or papules to highly deformative plaques that are thickened and hyperkeratotic [24]
Acknowledgements
The authors would like to sincerely thank the South African Medical Research Council (Flagship program MalTB Redox), the Centre of Excellence for Pharmaceutical Sciences, Faculty of Health Sciences, North-West University, South Africa. Any opinion, findings and conclusions or recommendations expressed in this material are those of the authors and therefore the NRF does not accept any liability in regard thereto.
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