Mycobacterial Skin Infections

The overview of mycobacterial skin infections presented in this work is justified by the current worldwide increase in diseases induced by both old and new mycobacteria. Until the late 1980s such diseases had been notably declining, but after that period the trend reversed and an exponential increase began to be observed. There are various reasons for this rise not only in developing countries but even in urban areas in the most developed nations. Being the cause of tuberculosis and leprosy, the Mycobacterium genus has probably caused mankind more suffering than all the other bacterial genera combined. Moreover, in addition to the obligate pathogens, namely the Mycobacterium tuberculosis complex and M. leprae, this genus is continually being enriched by the addition of many other species. Although usually encountered as environmental saprophytes, in some conditions that depend on the host immune status they can induce extremely severe, sometimes fatal clinical pictures. It is well known that tuberculosis (TB) is one of the oldest diseases ever to affect mankind, but nowadays it is emerging once more as an enormous and growing global health problem. According to the World Health Organization (WHO) (Global Tuberculosis Report 2016, World Health Organization), in 2015 there were an estimated 10.4 million new (incident) TB cases worldwide, of which 6.9 million (56%) were among men, 3.5 million (34%) among women and 1.0 million (10%) among children. HIV-infected people accounted for 60% of al new TB cases. Six countries accounted for 60% of the new cases: in descending order, India, Indonesia, China, Nigeria, Pakistan, and South Africa. The rate of decline in TB incidence remained worldwide at only 1.5% from 2014 to 2015. This need to accelerate to a 4.5 % annual decline by 2020 to reach the first milestones of the End TB Strategy. The WHO End TB Strategy (approved by the World Health Organization in 2014), in fact, calls for a 90 % reduction in TB deaths and an 80% reduction on the TB incidence rate by 2030, compared with 2015. According to many authors, the high present TB incidence is attributable to increased levels of poverty in our over populated world, to the breakdown of health care systems and to the impact of the HIV/AIDS pandemic. Further complicating the situation, there has been a worrying rise in multidrug-resistant TB (MDR-TB) (defined as resistance to isoniazid and rifampicin), and now we also face the recent emergence of extensively drug-resistant TB (defined as resistance to many other drugs). In 2015, there were an estimated 580.000 new cases of MDR-TB. India, China and Russian Federation accounted for 45% of the combined total of 580.000 cases. The WHO estimated that in 2015 there has been 1.4 million TB deaths, and an additional 0.4 million deaths resulting from TB infection among HIV-infected people. Although the number of TB deaths fall by 22% between 2000 and 2015, TB remained one of the top 10 causes of death worldwide in 2015. Extra-pulmonary disease TB manifests only in 8.4-13.7% of cases, while cutaneous TB comprises only a small proportion (< 1%-2%) of all cases of TB. All the same, in view of the current high prevalence of TB worldwide these numbers become significant. Assuming that 1% of all cases of TB will have cutaneous involvement, dermatologists in countries such as India, for example, where 1,847,000 new cases of TB were reported in 1999, must expect to see an annual incidence of about 18,000 cases of cutaneous TB. In any event, factors such as HIV infection and migration are ensuring that cutaneous TB will necessarily have to be included in differential diagnosis made by dermatologists all over the world. Apart from by M. tuberculosis, TB in man is induced also by M. bovis, that has a greater number of potential hosts than the tubercle bacillus. Various studies have shown that 0.3 to 1.5% of TB in humans is due to M. bovis in developed countries. Due to inappropriate methods for identifying the pathogen, in developing countries the incidence is unknown, but is most likely higher than in industrialized countries. In 1992, the European Union declared infection by M. bovis one of the 4 most important zoonoses (European Union. Council directive 29/117/EEC, 1992. Off J Eur Comm 1993; L62:38), and in 1995 the WHO labeled the infection a global emergency (Guidelines for speciation within the Mycobacterium tuberculosis complex. Geneva: World Health Organization, 1995). Among the various modes of transmission of this organism to man (respiratory, gastrointestinal) we must include direct skin contact, that occurs mainly in some occupational fields. Meanwhile, the modes of transmission of M. leprae are still not fully understood. There is solid evidence of transmission among contacts, as well as of zoonotic leprosy in southern states in the United States of America. Current findings suggest that aerosols/droplets and shedding of bacteria in the environment, as well as skin-to-skin contact, are possible culprits. Globally, the number of leprosy cases is now below the elimination threshold of 1 case/10,000 people, as defined by the WHO. In various countries and sub-national regions, however, the number of leprosy patients is still above this threshold. Moreover, despite the near-universal use and efficacy of multidrug therapy, the annual number of newly detected cases has remained fairly constant at around 200,000-300,000 cases in the last years. This demonstrates that the current control measures are insufficient to arrest the process of leprosy transmission. The experience we gained over several years of assiduous attendance of the Hansenian Colony in Gioia del Colle (Bari, Italy), one of the largest in Europe, validated by clinical-therapeutic studies of the disease, has been of inestimable aid in writing the relative chapter about leprosy. To compound the issue, nontuberculous mycobacteria (NMT) are common in nature and, except perhaps in extreme environments such as deserts and polar regions, humans are regularly exposed to them. Unlike the obligate pathogens, NMT may occur as transient commensals on the skin and in various other organs (the pharynx, lower urethra, gastrointestinal tract), so their isolation does not necessarily indicate the presence of disease. The pathogenicity of NTM is directly correlated to the host immune system and in fact, since the 1930s many species have been strongly associated with some human diseases. The development of new diagnostic tools has resulted in a huge increase in the number of infections associated with specific species, as well as the number of new species identified as causal agents. NTM can cause a vast spectrum of diseases, that are often quite difficult to diagnose. A high suspicion index is important, and the diagnostic conclusions must be based on a number of microbiological and radiological investigations. It must also be borne in mind that the search for bacilli in the various clinical specimens may not always be positive. Even histopathology is not definitive because granulomatous tubercle findings are rare whereas nonspecific inflammatory aspects are common. The aim of this work is, therefore, to offer dermatologists a tool to help them recognize the different clinical mycobacterial manifestations, make a prompt diagnosis, and institute effective treatment. Unfortunately, older dermatologists tend to have become less familiar with these very important diseases in recent decades, while younger dermatologists have perhaps never encountered them before. By contrast, the current globalization process, and all its accompanying implications as regards infectious diseases that may be more or less widespread in the different countries, “demands” as wide as possible a knowledge of these among clinicians. Bari, Italy