Cutaneous candidiasis is one of the types of infection caused by Candida albicans, one of the most common fungal pathogens encountered worldwide. Patients frequently have some preexisting form of immunodeficiency that predisposes them to this infection. Most commonly, the intertriginous and interdigital areas are affected. The diagnosis is made clinically and confirmed by microscopic examination and culture, while treatment includes administration of both topical and oral antifungal agents.
Presentation
The clinical presentation of patients with cutaneous candidiasis may significantly vary depending on the site of infection. Three distinct forms exist [9]:
- Intertriginous infection - In these patients, an infection occurs in intertriginous areas, such as the inframammary, axillary, perineal, and groin region. On clinical examination, erythema of the skin and overlying eroded confluent pustules are observed, eventually transforming into eroded patches with adjacent small pustules (termed "satellite pustules").
- Interdigital infection - This form is most commonly observed among obese individuals, and the infection develops in the interdigital region of both the hands and the feet. Similar findings may be obtained, such as the presence of erythema and eroded pustules, but white thickening of the skin is commonly observed.
- Diaper dermatitis - This term describes that cutaneous candidiasis may occur in neonates and infants as a result of favorable moist conditions for growth of this fungal pathogen in the perineal area [10]. The buttocks may be affected as well, and significant erythema, papules, pustules, erosions and scaling may be observed.
Workup
Once the suspicion toward cutaneous candidiasis has been made, the diagnostic workup should include laboratory testing to evaluate the status of the immune system, while a definite diagnosis is made by performing microscopy examination and culture from obtained tissue samples [11].
Because infection by Candida species usually implies that the patient may have some underlying condition which may impair the normal function of the immune system, a laboratory evaluation, including complete blood count (CBC), blood glucose levels, and basic biochemical tests should be performed. Lactate dehydrogenase (LDH), liver transaminases (including ALT and AST), serum electrolytes (Na, K, Cl, Ca) should be assessed, especially in patients who report other complaints, such as fever, cough, headaches and other symptoms that possibly indicate a systemic disease.
Microscopic evaluation and culture are gold standards in the diagnosis of cutaneous candidiasis. Cutaneous lesions are scraped to obtain a valid material for examination, and subsequent potassium hydroxide (KOH) preparation shows budding yeasts on microscopy [12]. Culture on standard fungal media will usually reveal Candida species, but this diagnostic method takes at least several days to yield results. Nevertheless, treatment may be started immediately after materials are obtained for cultivation.
Treatment
Treatment of cutaneous candidiasis comprises topical administration of antifungal agents and in some cases, corticosteroid preparations.
Several agents have been recommended for topical use [13]:
- Imidazole creams, including clotrimazole, miconazole, econazole, usually q6-8h for 7-14 days.
- Nystatin - A Candida-specific antifungal agent is also used q6-8h for 7-14 days.
- Ciclopirox olamine 1% cream has also been used in the treatment of fungal skin infections, and it is applied 2x daily for 7-14 days.
- Corticosteroid preparations have been proposed as adjuvant regimens, but antifungal agents show much better results, as they act directly on the cause.
In severe cases of diaper dermatitis, or recurrent cutaneous infections, oral administration of ketoconazole 400 mg q24h for 14 days is recommended, while other agents may be included in therapy if there is a concomitant presence of candidiasis in other regions.
Prognosis
The prognosis is generally good, patients can be effectively treated, but recurrent infections may be present. In cases of immunodeficiency, the possibility of systemic infections poses a significant danger to the patient health. For these reasons, it is imperative to make a prompt diagnosis and start treatment as soon as possible.
Etiology
Candida albicans belongs to the Candida genus, along with several other species, including C. glabrata, C. parapsilosis, C. tropicalis and other. It exists in oval yeastlike forms, up to 5 µm in diameter, and produces pseudohyphae and hyphae. Additionally, C. albicans has the ability to form germ tubes [3], which are constituents of its growth.
Epidemiology
Candida albicans is a ubiquitous microorganism and it is found in soil, water and can live in various animals, but most importantly, it commonly resides in humans. C. albicans is considered to be a part of the normal flora of the oral cavity and the gastrointestinal tract in a substantial percent of people, and it is also commonly found on the skin [4]. It is established that patients develop an infection, including cutaneous forms, from Candida microorganism that is already present in the body or on the skin, which is why it is often considered an endogenous infection.
The exact prevalence rates of cutaneous candidiasis are not known, but certain studies indicate that it is responsible for about 7% of all dermatology consultations [5]. However, other studies indicate that cutaneous candidiasis is rarely encountered, less than 1% [6], which implies that epidemiological data vary significantly.
In order for C. albicans to establish an infection in the human host, some form of immune deficiency must exist, since infections by this fungus are rarely reported in immunocompetent individuals. Significant increases in the number of infections caused by Candida species have been observed throughout the last few decades, supposedly because novel treatment strategies for severe and chronic illnesses have some impact on the development of the infection. The most important risk factor for the development of cutaneous candidiasis is diabetes mellitus, while other risk factors that predispose individuals to cutaneous, but also various other forms of candidiasis include HIV infection, immunosuppressive therapy, organ transplantation, a presence of malignant diseases, etc. Advanced age has also been determined as a risk factor, while iatrogenic factors also play a role in predisposing patients to candidiasis. Use of certain antibiotics, such as tetracycline, trimethoprim-sulfamethoxazole and doxycycline have shown correlations with increased risk for infections caused by Candida species.
Pathophysiology
Normally, the immune system, including neutrophils, macrophages, lymphocytes and components of the innate defense mechanism, such as the complement system and dendritic cells, are able to keep Candida albicans away from causing harm to the human host [7]. Dendritic cells belong to the group of antigen-presenting cells (APCs), and once they encounter Candida microorganism attempting to penetrate the skin, or in circulation, several pathways are triggered. Complement activation, mobilization of neutrophils, eosinophils and macrophages mediated by CD4+ T-helper cells, and activation of various proinflammatory cytokines occurs. Interleukins, including IL-4, IL-12 and IL-17, interferon gamma (IFN-γ), and many other are activated to induce a proper immune response against this fungal pathogen, and they do so in a successful manner in an immunocompetent host.
However, under circumstances of immunodeficiency, or in the case of cutaneous candidiasis, damage of the skin and mucosa, the fungus may proliferate and establish an infection [8]. Neutrophil functions are impaired in patients with diabetes mellitus, while CD4+ T-helper cells are deficient in patients with HIV infection. On the other hand, granulocyte function is reduced by certain antibiotics, making the immune system unable to eradicate C. albicans. In addition to impaired host defenses, several virulence factors have been established, such as proteases, phospholipases, a presence of human-like integrins, which are molecules used for cellular adhesion and perform various other functions that aid C. albicans in infecting the human host.
Prevention
Significant steps in preventing cutaneous candidiasis can be made [14]. Strategies that have proven to be of benefit include avoidance of broad-spectrum antimicrobial agents such as tetracycline in patients with underlying immunosuppression, making sure intertriginous regions are dry and proper skin care.
Summary
Cutaneous candidiasis is a skin infection caused by Candida albicans, a commensal and ubiquitous microorganism that triggers various types of infections worldwide. Candida is one of the most common fungal microorganisms encountered in medical practice and cutaneous infections can appear in several forms. Since this organism is readily found on the skin of healthy individuals (and also comprises normal flora of the oral cavity and the gastrointestinal tract), some predisposing condition which lowers the immune defense, which consequently puts individuals at risk, is almost always found [1]. One of the most important risk factors for a development of cutaneous candidiasis is diabetes mellitus, while other risk factors include human immunodeficiency virus (HIV) infection, immunomodulating therapy and organ transplantation. Iatrogenic causes may also contribute, such as the use of antibiotics and corticosteroids, while instrumentation and presence of indwelling catheters are a risk for not only cutaneous but systemic forms of disease as well. The location of a clinical presentation can involve intertriginous areas, such as the inframammary, perineal and axillary regions, as well as the groins. Candida albicans is one of the causes of intertrigo, with erythema, pruritus, and pain as main features [2]. Interdigital presentation involves a development of eroded pustules and scaling on both the hands and feet. Diaper dermatitis, characterized by erythema, papules, and pustules seen in neonates and infants can also be a manifestation of this infection. The diagnosis of cutaneous candidiasis is made clinically, during a physical examination, while a definite diagnosis is made by microscopy and culture of the sampled material. Treatment involves topical administration of antifungal agents, such as nystatin and imidazole, while corticosteroids may be helpful as well. In severe cases of diaper dermatitis or recurrent infection in the perineal and genital areas, oral nystatin may be helpful. Significant steps in prevention of this infection can be made, through keeping intertriginous areas dry and use of imidazole powder in susceptible individuals.
Patient Information
Cutaneous candidiasis is an infection of the skin by a fungus called Candida albicans, which is one of the most common fungi responsible for infection in the human population. Candida albicans is ubiquitous and is readily found in soil, water, animals and even comprises normal flora of the gastrointestinal tract in a substantial number of humans. More importantly, this fungus can be found on the skin in many healthy individuals, which indicates that Candida albicans may be a part of normal skin flora as well. Cutaneous candidiasis is rarely seen in immunocompetent individuals and it is established that patients who have an infection caused by Candida albicans almost always have some underlying condition which impairs their immune system. Diabetes mellitus, human immunodeficiency virus (HIV) infection, or chronic use of certain medications, such as corticosteroids and immunosuppressants may predispose individuals to candidiasis. Certain antibiotics such as tetracycline may also impede normal immune mechanisms. There are three distinct forms of cutaneous candidiasis - Infection of the intertriginous areas (known as intertrigo), infection of spaces between the fingers (interdigital infection) and diaper dermatitis (implying infection in newborns and infants on the buttocks and genitals in moist areas under the diaper). In these patients, the infection presents with a red rash consisting of lesions over the level of the skin that erode and occasionally crust, while the redness presents in confluent fashion. The presumptive diagnosis is made during clinical examination, while a definite diagnosis is obtained by scraping the site of the rash swabs, obtaining material for microscopic examination and culture. Treatment includes topical use of antifungal agents, such as nystatin, clotrimazole, and miconazole, which are applied 3-4 times during the day for one or two weeks, depending on the severity of an infection. It is important to evaluate patients for underlying conditions that may predispose them to infections caused by candida, including blood glucose levels and white blood cell count. In general, patients recover from this infection without any sequelae, but recurrences may occur. In rare cases, patients may have additional symptoms that include systemic infection by Candida microorganism, which can present a significant danger to the patient's health. For these reasons, prompt diagnosis and treatment are necessary. Some preventive strategies that have proven to be effective, which is especially important for patients who are at risk for this type of infection, such as immunocompromised patients, include proper hygiene and keeping intertriginous areas as dry as possible. In certain cases, antifungal imidazole powder could be used on a daily basis.
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