Cutaneous tuberculosis overview and current treatment regimens

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 [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.