Owing to the wide variety of possible causes, skin infections clinically present in a heterogenous manner and only few aspects can be generalized: Usually, a skin infection triggers an immune response, and the interactions between the causative pathogens and the patient's immune system result in an inflammation. The latter is characterized by the five cardinal signs of inflammation, i.e., by calor, dolor, rubor, tumor and functio laesa. Additionally, molecules released by microorganisms or the body's own immune cells may mediate systemic effects. Moderate to severe skin infections may thus be associated with fever, chills, hypotension and tachycardia. Streptococcus pyogenes is very likely to induce such systemic symptoms, which is reflected in its name.

Patients presenting with dermatological lesions should undergo a thorough general and dermatological examination. This approach does not only aim at clarifying whether a patient suffers from a skin infection or not, it may also allow to recognize signs indicating an underlying disease. As has been mentioned above, immunodeficient patients are at particularly high risks of contracting infectious diseases, and immunodeficiency may be caused by diseases as common as diabetes mellitus [10]. The presence of primary disorders may also affect the choice of treatment [11].

In most cases, skin infections are diagnosed clinically. The patient's response to empirical treatment may then confirm this diagnosis, or indicate the need for further diagnostic measures. It is not generally recommended to delay treatment until the causative pathogen has been isolated and defined. In moderate to severe cases, however, representative specimens should be obtained before antimicrobials are administered. If they are tested for the presence of determined microorganisms, the respective results may already be available when a change of the therapeutic regimen is required. In detail, the following techniques may be applied:

• Gram staining and microscopic examination of samples
• Isolation of pathogens and evaluation of resistance to antimicrobials
• Immunoassays
• Serological tests
• Molecular biological tests like polymerase chain reaction
• Histopathological analysis of tissue samples

Treatment primarily aims at eliminating the causative pathogen, but appropriate wound care is also indicated. Either systemic and topical treatment may be indicated, depending on the extension of the dermatological lesion.

If a bacterial skin infection is suspected and an antibiogram is not yet available, antibiotics with known effectivity against Gram-positive, lactamase-resistant strains should be applied. Cephalosporins and fluoroquinolones are most frequently used, but bacteria may present with resistances to those compounds in certain geographic regions. Thus, knowledge about the local resistance situation is required to take this decision. Particular care has to be taken if a patient proves to be infected with methicillin-resistant Staphylococcus aureus. A total of more than twenty pharmacological agents are approved for the therapy of skin infections, with vancomycin, ceftaroline, tedizolid, dalbavancin, oritavancin, and telavancin being active against methicillin-resistant strains [12].

Infections with fungi are treated with antimycotics, e.g., with azoles like miconazole, ketoconazole, itraconazole or fluconazole, with terbinafine, or with amorolfine [13]. Otherwise, recommendations are similar to those given above. Antifungal therapy may also be administered systemically or topically.

Antiviral therapy, preferentially with acyclovir, is required if the patient suffers from an infection with Herpesviridae, Poxviridae or other viral pathogens.

Some skin infections may require incision and drainage or even more extensive surgery.

The majority of skin infections are associated with a good to excellent prognosis, depending on the availability of proper medical attention. However, even well-treatable skin infections may considerable limit the patient's life quality. Pain, pruritus and psychological burden are only three examples for symptoms related to dermatological disorders that may interfere with carrying out everyday tasks and maintaining an active social life.

Few skin infections are life-threatening, e.g., the above mentioned staphylococcal scalded skin syndrome, but mortality may also be registered in patients suffering from seemingly uncomplicated infections with multiresistant pathogens.

Even under physiological conditions, many species of microorganisms colonize the human skin. Here, it is important to distinguish a colonization from an infection: A person does benefit from the presence of several microorganisms on their skin, while others are rather classified as commensals. The entirety of those microorganisms constitutes the physiological skin flora, and its composition varies depending on the precise area of skin in question, on endogenous host factors and exogenous environmental factors. In general, species pertaining to bacterial genres Corynebacterium, Propionibacterium and Staphylococcus are most abundant [1]. With regards to fungi, Malassezia spp. dominate the microbiome. Little is known about viruses being part of the skin flora.

Moreover, the skin disposes of non-specific and specific defense mechanisms to prevent a skin infection. Keratinocytes, for instance, may release antimicrobial peptides and cytokines, namely defensins, histatins and cathelicidin as well as IL-1β, IL-6, IL-10 and TNF-α, among others [2] [3] Some are released constitutively, others upon stimulation by microbial structures or pro-inflammatory cytokines.

In sum, for a skin infection to take place, one or more of the following conditions need to be fulfilled:

• Breakdown of physical barrier, e.g., in case of wounds
• Deficiency of non-specific or specific immunity
• Highly virulent pathogen or large infectious dose

A complete list of possible etiologic agents cannot be provided, but some examples shall be given:

• Staphylococcus aureus, including methicillin-resistant strains
• β-hemolytic Streptococcus spp.
• Dermatophytes like Trichophyton spp. and Microsporum canis
• Yeasts like Candida spp. and Malassezia spp.
• Herpes simplex virus and varicella zoster virus
• Human papillomavirus
• Molluscum contagiosum virus and other Poxviridae

In general, skin infections are very common and may affect men and women, people of all races and age groups. However, incidence, prevalence and distribution of determined skin infections vary significantly. Tinea pedis is a dermatophytic infection of interdigital areas of the foot, and the disease' prevalence has been reported to be about 3% in the general population and up to 60% in selected populations at high risks [4]. Incidence rates increase with age and men are affected more often than women. Similarly high prevalence rates have been reported for impetigo, a disease caused by an infection with Gram-positive cocci: In Australia and Oceania, approximately 40% of the population show signs of impetigo [5]. On the other hand, Staphylococcus aureus may induce staphylococcal scalded skin syndrome, a rare type of skin infection typically diagnosed in neonates and infants. This life-threatening disease only affects about 1 in 10,000,000 habitants per year [6].

Both from an epidemiological and a clinical point of view, the increased incidence of skin infections with methicillin-resistant Staphylococcus aureus is alarming [7].

The skin is composed of epidermis and dermis as well as skin appendages like sweat glands, sebaceous glands, hairs and nails. For pathogens to reach deeper layers of the skin, they need to overcome the epidermis. This is most easily done if the patient presents a cut or laceration, or an insect bite. However, the precise point of entry is not always traceable.

Distinct medical terms have been coined to describe skin infections that compromise its individual components, and those terms may already imply if an infection is mild or severe, if its acute or chronic. The following list shall serve as an orientation to this end:

• Impetigo is a superficial skin infection mainly diagnosed in pediatric patients. Staphylococcus aureus is the causative pathogen of bullous impetigo; β-hemolytic Streptococcus spp., mainly Streptococcus pyogenes, cause non-bullous impetigo.
• If not adequately cared for, impetigo may turn into ecthyma, a type of skin infection that extends into the dermal layer. Lesions are often covered by eschar-like indurated plaques. Development of ecthyma is frequently associated with occlusion of impetigo, poor general hygiene and immunodeficiency due to malnutrition.
• Erysipelas also refers to an infection of the upper layers of the skin, but this type of skin infection involves lesions of lymphatic vessels. It is most frequently caused by Streptococcus pyogenes, and other β-hemolytic Streptococcus spp. play minor roles in erysipelas etiology.
• Cellulitis refers to a poorly demarcated inflammation of the dermis and subcutaneous tissues, and pathogens usually enter through damaged skin. Of note, pathogens may also cause cellulitis after hematogenous or lymphatic spread from distant foci of infection. The most common etiologic agents of cellulitis are β-hemolytic Streptococcus spp. and Staphylococcus aureus [8].
• Pyoderma is a deep skin infection associated with pus formation. Similar to the aforedescribed conditions, Gram-positive cocci account for the majority of pyoderma cases. Of note, pyoderma gangrenosum is a skin disease of unknown etiology. It is marked by deep ulcers and necrotizing areas, but intents to isolate causative pathogens usually yield negative results.
• Folliculitis describes an inflammation of hair follicles; it is most commonly caused by an infection with Staphylococcus aureus, Pseudomonas aeruginosa or fungi. Accordingly, folliculitis can be detected in patients suffering from tinea capitis, tinea corporis and tinea pedis, among others.
• Purulent inflammation of hair follicles and development of small abscesses characterize furunculosis [9].
• Warts are the result of benign epithelial growth triggered by an infection with human papillomavirus, which is largely facilitated by pre-existing epithelial lesions.

All measures aiming at the preservation of the integrity of the skin and a strong immune system may help to reduce the individual risk of skin infections. With regards to the former, both a lack of skin hygiene as well as an excess to this effect may have detrimental consequences. The physiological skin flora protects from infections by means of competitive exclusion. Thus, alterations of the normal microbiome may predispose for skin infections.

Moreover, direct contact to contaminated skin or surfaces should be avoided. To this end, it is recommended to cover wounds, not to share personal hygiene products, to wash hands regularly, and to use disinfectants when necessary.

The skin is the human's largest organ and covers an area of approximately 1.8 square meters in adults [1]. It fulfills a myriad of functions, one of them being to protect the human body from noxious agents present in its environment. Since the skin constitutes the interface with the outside world, it is continuously exposed to such noxious agents, e.g., to bacterial, fungal or viral microorganisms. Under determined conditions, which are discussed further in the following sections of this article, those microorganisms may invade the patient's skin and start to multiply in excess. This way, a skin infection develops.

The vast majority of skin infections are not life-threatening, but they may considerably restrict the patient's quality of life. Their diagnosis is usually based on physical examination alone, and treatment is often chosen empirically. And indeed, this rapid, low-cost approach to therapy may work since most types of skin infection are caused by only few distinct pathogens. However, it also bears the risk of misdiagnosis, inappropriate treatment and spread of infection. Thus, further diagnostic measures are indicated in case of severe skin infections, e.g., isolation and determination of the causative pathogen and histopathological analysis of skin biopsy samples.

Skin infection is a very general term; it refers to the invasion and multiplication of pathogens within the patient's skin. Skin infections may be provoked by bacteria, fungi and viruses, whereby the most common causative agents are Staphylococcus aureus, Streptococcus spp., and dermatophytes. Distinct skin infections vary largely regarding their manifestation, their severity and extension, as well as their distribution across the population.

Some types of skin infection are very common, e.g., impetigo, superficial, bacterial infection mainly diagnosed in pediatric patients, and tinea pedis, which is also known as "athlete's foot"; others are rare. Although few skin infections are life-threatening, pain, pruritus and psychological stress associated with such diseases may considerably reduce the patient's quality of life. The vast majority of those infections is curable, but affected individuals tend to delay medical checks until the infection spread. This behavior leads to prolonged treatment times, higher costs and possibly a worse prognosis. Thus, it is recommended to consult a physician in a timely manner, and to learn about possible preventive measures. The physician may clear any doubts regarding a proper skin hygiene.

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