Dermatovenerological infections

In dermatology, infections caused by bacteria, viruses, fungi, and parasites play an important role. A large proportion of pathogen‐related infections of the skin and mucous membranes are transmitted sexually. All areas of infectious diseases and dermatovenerology are subject to highly exciting, dynamic change. This is driven by changes in the epidemiology of long‐established diseases, changes in the resistance of pathogens to anti‐infectives, recurrence of known pathogens, and the emergence of completely new pathogens. In this article, we address “resistance to anti‐infectives”, “sexually transmitted infections”, and “emerging viral infections”, three core areas of dermatovenerology that will shape the field in the years to come.


INTRODUCTION
Infectious dermatoses are seen very frequently in clinical practice. This field of dermatology is highly dynamic and fascinating, not least due to geographic and demographic changes and widespread traveling activities. In the last few years, we have repeatedly encountered skin manifestations which were unusual or even completely new to us. In the context of the war in Syria since 2010, for example, the number of diagnosed cases of leishmaniasis has risen sharply, 1 and since 2016 we have suddenly started to see eruptions caused by Zika virus in the context of a large international outbreak. 2 A significant number of Covid-19-associated skin manifestations have also been reported, 3,4 and in 2022 a new sexually transmitted disease version of "monkeypox" showed clinical manifestations never described before. 5 Looking to the future, we can say with confidence that dermato-infectiology will remain a challenging field given the recent dynamics. Resistance to antimicrobials, sexually transmitted infections (STIs), and new viral infections, as well as additional rare infections, will certainly constitute central topics also in the German-speaking countries.

RESISTANCE TO ANTIMICROBIAL AGENTS
The World Health Organization (WHO) considers resistance to antimicrobial agents (AMR; anti-microbial resistance) one of the ten most important threats to global health. 6 The ability to develop resistance against antibiotics is a natural phenomenon but is massively aided by the use and especially misuse of antibiotics. In our medical field, pathogens such as Staphylococcus (S.) aureus and Pseudomonas aeruginosa but also Neisseria gonorrhoeae und Mycoplasma genitalium are especially challenging. Resistant dermatophytes constitute a new development. Trichophyton indotineae, for example, is a very recently identified variation of dermatophytes which was first found on the Indian sub-continent, almost epidemically, but has now started to spread to other parts of the world. 7 Infection with this pathogen is characterized by extensive, pruritic inflammation in the inguinal region as well as on the buttocks, the trunk, and the face. 7 Patient of all ages and sexes may be affected, and the pathogen is resistant to terbinafine. 7 In the German-speaking countries, however, multiresistant pathogens currently play only a minor role for most dermatological infections seen in day-to-day practice. In its yearly epidemiological report from 2020, the European Centre for Disease Prevention and Control also stated that methicillin-resistant isolates of S. aureus decreased between 2016 and 2020. This carries a risk that we underestimate the problem of AMR. Data from the United States show that dermatology, as compared with other medical specialties, is the field in which antibiotics are most frequently prescribed. 8 This promotes the development of multidrug-resistant pathogens not only on the skin. Systemic antibiotics, of course, affect not only bacteria on the skin but also in other regions of the body such as the gut. When dermatologists prescribe antibiotics, they contribute to the development of resistance in other bacterial strains, including highly problematic Klebsiella pneumoniae or Escherichia coli.
In the field of dermatovenereology, there are four large areas, where antibiotics are prescribed routinely, often also as oral medications in an outpatient setting: (1) simple cutaneous infections (such as impetigo, small abscesses, erysipelas), (2) in the context of skin surgery, (3) inflammatory dermatoses such as inverse acne, acne vulgaris, rosacea, bullous pemphigoid, 9 and (4) STIs. In each of these areas, it will be essential to utilize antibiotic treatment with critical reflection and in an optimized manner. For cutaneous infections, in addition to adequate diagnostics, targeted, "narrow", and temporally optimized antibiotic treatment according to the current guidelines is essential. Classic examples include the treatment of erysipelas caused by group A streptococci with penicillin, 10 or a singledose treatment with ceftriaxone for gonorrhea. 11 We need rigorous concepts for perioperative antibiotic administration, such as a single, targeted perioperative application for high-risk surgeries, and refrainment from prolonged treatment with antibiotics without signs of infection. 12 For inflammatory dermatoses, alternative treatments such as biologics in inverse acne offer the potential for saving on antibiotics. 9 In all of these areas, we see a high need for further research as well as for the development and application of guidelines to ensure optimum use of antibiotics. In addition, other therapeutic approaches such as reinforcement of the immune system, host-specific treatments, and passive antibody treatments will gain importance in the future.

SEXUALLY TRANSMITTED INFECTIONS
STIs are a central part of our medical field -not only from a historical point of view, but also because they reflect the rapid evolvement of dermatological infectiology as demonstrated by the high dynamics of newly emerging pathogens, 13 antimicrobial resistance, and diagnostic and therapeutic advances. 14 STIs are defined as infections that are mainly transmitted via sexual contact, even though other close physical contacts may be sufficient for transmission of some pathogens. 15 They can be caused by a large number of bacteria, viruses, fungi, protozoa, and arthropods, and in a broader sense STIs also include enteric pathogens such as shigella, hepatitis A virus, campylobacter, or newly emerging viral infections such as Zika virus or Ebola virus. 16,17 Infections with herpes simplex virus (HSV) and human papillomavirus (HPV) show a high prevalence in the general population and may cause persistent or recurring complaints. 18,19 While superficial infections with chlamydia trachomatis are especially common in young men and women, other STIs such as lymphogranuloma venereum as well as the newly discovered monkeypox virus are mainly found in men who have sex with men. 20 The consequences of STIs are numerous and associated with a high economic burden on the healthcare system. 21 Sexual and reproductive health are frequently affected, and this may be transient or persistent depending on the pathogen in question. 22,23 STIs such as syphilis, gonorrhea, or Human Immunodeficiency Virus (HIV) may also be passed from a mother to her neonate. The contemporary relevance of this serious problem is demonstrated by the fact that some countries are reporting an increase of congenital syphilis, underscoring the importance of screening for syphilis during pregnancy. 24 HPV infections may be associated with both benign and malignant lesions on the skin and mucous membranes, and are in fact the most common cause for genital carcinomas. Especially in immunocompromised patients with a decrease in the protective immune response of the mucous membranes, such as in HIV patients, a high incidence of malignant, HPV-associated neoplasia has been reported. 25,26 Despite the high efficacy of the HPV vaccine which protects against nine types of HPV, HPV-associated lesions on the mucous membranes still remain a common and sometimes challenging problem in our day-to-day practice. Genital inflammation caused by STI also leads to an increase risk of HIV infection. Since patients with high-risk behavior are frequently affected by HIV as well as other STIs, enhanced HIV transmission is a common problem. 27 Resistance to antibiotics is widespread in STIs, particularly in the case of Neisseria gonorrhoeae and Mycoplasma genitalium, 28 two types of bacteria that cause urethritis. But even in viral pathogens such as HIV or HSV, resistance against anti-infective medications may cause therapeutic problems. For this reason, careful monitoring of the development of resistance is essential to ensure a rapid response. In this context, we would like to stress the importance of gonococcal cultures that enable a rapid response to changes in resistance patterns. Amplification procedures are available for Mycoplasma genitalium that can also detect macrolide resistance, which is particularly important since this type of resistance is common.
Despite significant progress in the treatment and diagnosis of STIs, it will be essential in the future to develop new vaccines against viruses (in addition to the established vaccines against HPV or hepatitis B) and bacteria. 29 Public awareness of STIs must also be improved.

EMERGING VIRAL INFECTIONS
Global warming and altered patterns of precipitation have led to the spreading of vectors such as mosquitoes, ticks, fleas, birds, and other animals that may transmit pathogens. 2 Combined with increased global travel and the ability of some viruses to infect different species, this constitutes an ever-increasing problem. Vector-transmitted flaviviruses such as Dengue, Zika, or West Nile virus are excellent examples of this phenomenon. 2 Due to the spread of Aedes mosquitoes, about a quarter of the global population now lives in areas where Dengue fever is endemic. Before the large outbreak in 2013/2014 with millions of infections, Zika virus was only seen sporadically. There have been reports that West Nile virus can now hibernate in German mosquito populations. 30 It seems entirely possible that some of these diseases will also become endemic in German-speaking countries.
Apart from the further spread of established pathogens, we can also expect an emergence of new viral infections. There are at least 10,000 viruses that can potentially infect humans. 31 The huge majority of these viruses, however, are currently 'mute' and circulate in wild animals only. 31 Nevertheless, due to climatic and geographic changes, we can assume that transmission of viruses between different species (zoonotic spillover) will increase, 31 and humans will not be exempt. The epidemic/pandemic outbreaks of Ebola virus, and presumably also SARS-CoV-2, are prominent examples. Interestingly, bats appear to play an important role in the spread of viral pathogens. This is due to their ability for widespread dispersion of viruses. 31

CONCLUSION
Infections of the skin and mucous membranes constitute an important aspect of dermatology and expand our medical field in various aspects. On the one hand, newly emerging or recurring pathogens require the development of appropriate therapeutic algorithms. At the same time, pathogens adapt to our treatments by developing resistance, so we must rapidly update our guidelines. In the last few years we have lived through a period where the influence of infectious disease has directly affected our daily life, and similar dynamics can be seen in STIs -not only in patient groups with high-risk behavior. New diagnostic, therapeutic, and preventative developments need to be accomplished to reduce the incidence of STI.