Candidiasis

Candidiasis
Synonyms Candidosis, moniliasis, oidiomycosis[1]
Oral candidiasis (thrush)
Specialty Infectious disease
Symptoms White patches or vaginal discharge, itchy[2][3]
Causes Candida (a type of yeast)[2]
Risk factors Immunosuppression (HIV/AIDS), diabetes, corticosteroids, antibiotic therapy[4]
Medication Clotrimazole, nystatin, fluconazole[5]
Frequency 6% of babies (mouth)[6] 75% of women at some time (vaginal)[7]

Candidiasis is a fungal infection due to any type of Candida (a type of yeast).[2] When it affects the mouth, it is commonly called thrush.[2] Signs and symptoms include white patches on the tongue or other areas of the mouth and throat.[3] Other symptoms may include soreness and problems swallowing.[3] When it affects the vagina, it is commonly called a yeast infection.[2] Signs and symptoms include genital itching, burning, and sometimes a white "cottage cheese-like" discharge from the vagina.[8] Less commonly the penis may be affected, resulting in itchiness.[3] Very rarely, the infection may becoming invasive, spreading to other parts of the body.[9] This may result in fevers along with other symptoms depending on the parts involved.[9]

More than 20 types of Candida can cause infection with Candida albicans being the most common.[2] Infections of the mouth are most common among children less than one month old, the elderly, and those with weak immune systems. Conditions that result in a weak immune system include HIV/AIDS, the medications used after organ transplantation, diabetes, and the use of corticosteroids. Other risks include dentures and following antibiotic therapy.[4] Vaginal infections occur more commonly during pregnancy, in those with weak immune systems, and following antibiotic use.[10] Risk factors for invasive candidiasis include being in an intensive care unit, following surgery, low birth weight infants, and those with weak immune systems.[11]

Efforts to prevent infections of the mouth include the use of chlorhexidine mouth wash in those with poor immune function and washing out the mouth following the use of inhaled steroids.[5] Little evidence supports probiotics for either prevention or treatment even among those with frequent vaginal infections.[12][13] For infections of the mouth, treatment with topical clotrimazole or nystatin is usually effective. By mouth or intravenous fluconazole, itraconazole, or amphotericin B may be used if these do not work.[5] A number of topical antifungal medications may be used for vaginal infections including clotrimazole.[14] In those with widespread disease, an echinocandin such as caspofungin or micafungin is used.[15] A number of weeks of intravenous amphotericin B may be used as an alternative.[15] In certain groups at very high risk, antifungal medications may be used preventatively.[11][15]

Infections of the mouth occur in about 6% of babies less than a month old. About 20% of those receiving chemotherapy for cancer and 20% of those with AIDS also develop the disease.[6] About three-quarters of women have at least one yeast infection at some time during their lives.[7] Widespread disease is rare except in those who have risk factors.[16]

Signs and symptoms

Skin candidiasis
Nail candidiasis (onychomycosis)
Vaginal yeast infection

Signs and symptoms of candidiasis vary depending on the area affected.[17] Most candidal infections result in minimal complications such as redness, itching, and discomfort, though complications may be severe or even fatal if left untreated in certain populations. In healthy (immunocompetent) persons, candidiasis is usually a localized infection of the skin, fingernails or toenails (onychomycosis), or mucosal membranes, including the oral cavity and pharynx (thrush), esophagus, and the genitalia (vagina, penis, etc.);[18][19][20] less commonly in healthy individuals, the gastrointestinal tract,[21][22][23] urinary tract,[21] and respiratory tract[21] are sites of candida infection.

In immunocompromised individuals, Candida infections in the esophagus occur more frequently than in healthy individuals and have a higher potential of becoming systemic, causing a much more serious condition, a fungemia called candidemia.[18][24][25] Symptoms of esophageal candidiasis include difficulty swallowing, painful swallowing, abdominal pain, nausea, and vomiting.[18][26]

Thrush is commonly seen in infants. It is not considered abnormal in infants unless it lasts longer than a few weeks.[27]

Infection of the vagina or vulva may cause severe itching, burning, soreness, irritation, and a whitish or whitish-gray cottage cheese-like discharge. Symptoms of infection of the male genitalia (balanitis thrush) include red skin around the head of the penis, swelling, irritation, itchiness and soreness of the head of the penis, thick, lumpy discharge under the foreskin, unpleasant odour, difficulty retracting the foreskin (phimosis), and pain when passing urine or during sex.[28]

Common symptoms of gastrointestinal candidiasis in healthy individuals are anal itching, belching, bloating, indigestion, nausea, diarrhea, gas, intestinal cramps, vomiting, and gastric ulcers.[21][22][23] Perianal candidiasis can cause anal itching; the lesion can be erythematous, papular, or ulcerative in appearance, and it is not considered to be a sexually transmissible disease.[29] Abnormal proliferation of the candida in the gut may lead to dysbiosis.[30] While it is not yet clear, this alteration may be the source of symptoms generally described as the irritable bowel syndrome,[31][32] and other gastrointestinal diseases.[22][33]

Causes

Candida yeasts are generally present in healthy humans, frequently part of the human body's normal oral and intestinal flora, and particularly on the skin; however, their growth is normally limited by the human immune system and by competition of other microorganisms, such as bacteria occupying the same locations in the human body.[34] Candida requires moisture for growth, notably on the skin.[35] For example, wearing wet swimwear for long periods of time is believed to be a risk factor.[36] In extreme cases, superficial infections of the skin or mucous membranes may enter into the bloodstream and cause systemic Candida infections.

Factors that increase the risk of candidiasis include HIV/AIDS, mononucleosis, cancer treatments, steroids, stress, antibiotic usage, diabetes, and nutrient deficiency. Hormone replacement therapy and infertility treatments may also be predisposing factors.[37] Treatment with antibiotics can lead to eliminating the yeast's natural competitors for resources in the oral and intestinal flora; thereby increasing the severity of the condition.[38] A weakened or undeveloped immune system or metabolic illnesses are significant predisposing factors of candidiasis.[39] Almost 15% of people with weakened immune systems develop a systemic illness caused by Candida species.[40] Diets high in simple carbohydrates have been found to affect rates of oral candidiases.[41]

C. albicans was isolated from the vaginas of 19% of apparently healthy women, i.e., those who experienced few or no symptoms of infection. External use of detergents or douches or internal disturbances (hormonal or physiological) can perturb the normal vaginal flora, consisting of lactic acid bacteria, such as lactobacilli, and result in an overgrowth of Candida cells, causing symptoms of infection, such as local inflammation.[42] Pregnancy and the use of oral contraceptives have been reported as risk factors.[43] Diabetes mellitus and the use of antibiotics are also linked to increased rates of yeast infections.[43]

In penile candidiasis, the causes include sexual intercourse with an infected individual, low immunity, antibiotics, and diabetes. Male genital yeast infections are less common, but a yeast infection on the penis caused from direct contact via sexual intercourse with an infected partner is not uncommon.[44]

Diagnosis

Agar plate culture of C. albicans
KOH test on a vaginal wet mount, showing slings of pseudohyphae of Candida albicans surrounded by round vaginal epithelial cells, conferring a diagnosis of candidal vulvovaginitis
Micrograph of esophageal candidiasis showing hyphae, biopsy specimen, PAS stain

Symptoms of vaginal candidiasis are also present in the more common bacterial vaginosis;[45] aerobic vaginitis is distinct and should be excluded in the differential diagnosis.[46] In a 2002 study, only 33% of women who were self-treating for a yeast infection actually had such an infection, while most had either bacterial vaginosis or a mixed-type infection.[47]

Diagnosis of a yeast infection is done either via microscopic examination or culturing. For identification by light microscopy, a scraping or swab of the affected area is placed on a microscope slide. A single drop of 10% potassium hydroxide (KOH) solution is then added to the specimen. The KOH dissolves the skin cells, but leaves the Candida cells intact, permitting visualization of pseudohyphae and budding yeast cells typical of many Candida species.

For the culturing method, a sterile swab is rubbed on the infected skin surface. The swab is then streaked on a culture medium. The culture is incubated at 37 °C (98.6 °F) for several days, to allow development of yeast or bacterial colonies. The characteristics (such as morphology and colour) of the colonies may allow initial diagnosis of the organism causing disease symptoms.[48]

Respiratory, gastrointestinal, and esophageal candidiasis require an endoscopy to diagnose.[23][49] For gastrointestinal candidiasis, it is necessary to obtain a 3–5 milliliter sample of fluid from the duodenum for fungal culture.[23] The diagnosis of gastrointestinal candidiasis is based upon the culture containing in excess of 1,000 colony-forming units per milliliter.[23]

Classification

Candidiasis may be divided into these types:

Prevention

A diet that supports the immune system and is not high in simple carbohydrates contributes to a healthy balance of the oral and intestinal flora.[34][41] While yeast infections are associated with diabetes, the level of blood sugar control may not affect the risk.[54] Wearing cotton underwear may help to reduce the risk of developing skin and vaginal yeast infections, along with not wearing wet clothes for long periods of time.[10][36]

Oral hygiene can help prevent oral candidiasis when people have a weakened immune system.[4] For people undergoing cancer treatment, chlorhexidine mouthwash can prevent or reduce thrush.[4] People who use inhaled corticosteroids can reduce the risk of developing oral candidiasis by rinsing the mouth with water or mouthwash after using the inhaler.[4]

For women who experience recurrent yeast infections, there is limited evidence that oral or intravaginal probiotics help to prevent future infections.[12][55] This includes either as pills or as yogurt.[12]

Treatment

Candidiasis is treated with antifungal medications; these include clotrimazole, nystatin, fluconazole, voriconazole, amphotericin B, and echinocandins.[15] Intravenous fluconazole or an intravenous echinocandin such as caspofungin are commonly used to treat immunocompromised or critically ill individuals.[15]

The 2016 revision of the clinical practice guideline for the management of candidiasis lists a large number of specific treatment regimens for Candida infections that involve different Candida species, forms of antifungal drug resistance, immune statuses, and infection localization and severity.[15] Gastrointestinal candidiasis in immunocompetent individuals is treated with 100–200 mg fluconazole per day for 2–3 weeks.[23]

Localized infection

Mouth and throat candidiasis are treated with antifungal medication. Oral candidiasis usually responds to topical treatments; otherwise, systemic antifungal medication may be needed for oral infections. Candidal skin infections in the skin folds (candidal intertrigo) typically respond well to topical antifungal treatments (e.g., nystatin or miconazole). Systemic treatment with antifungals by mouth is reserved for severe cases or if treatment with topical therapy is unsuccessful. Candida esophagitis may be treated orally or intravenously; for severe or azole-resistant esophageal candidiasis, treatment with amphotericin B may be necessary.[5]

Vaginal yeast infections are typically treated with topical antifungal agents.[15] A one-time dose of fluconazole is 90% effective in treating a vaginal yeast infection.[56] For severe nonrecurring cases, several doses of fluconazole is recommended.[15] Local treatment may include vaginal suppositories or medicated douches. Other types of yeast infections require different dosing. Gentian violet can be used for thrush in breastfeeding babies. C. albicans can develop resistance to fluconazole, this being more of an issue in those with HIV/AIDS who are often treated with multiple courses of fluconazole for recurrent oral infections.[57]

For vaginal yeast infection in pregnancy, topical imidazole or triazole antifungals are considered the therapy of choice owing to available safety data.[58] Systemic absorption of these topical formulations is minimal, posing little risk of transplacental transfer.[58] In vaginal yeast infection in pregnancy, treatment with topical azole antifungals is recommended for 7 days instead of a shorter duration.[58]

No benefit from probiotics has been found for active infections.[13]

Blood infection

Systemic candidiasis occurs when Candida yeast enters the bloodstream and may spread (becoming disseminated candidiasis) to other organs, including the central nervous system, kidneys, liver, bones, muscles, joints, spleen, or eyes. Treatment typically consists of oral or intravenous antifungal medications.[59] In candidal infections of the blood, intravenous fluconazole or an echinocandin such as caspofungin may be used.[15] Amphotericin B is another option.[15]

Prognosis

Among individuals being treated in intensive care units, the mortality rate is about 30-50% when systemic candidiasis develops.[60]

Epidemiology

Oral candidiasis is the most common fungal infection of the mouth,[61] and it also represents the most common opportunistic oral infection in humans.[62] In the Western Hemisphere, about 75% of females are affected at some time in their lives with a vaginal yeast infection.

Esophageal candidiasis is the most common esophageal infection in persons with AIDS and accounts for about 50% of all esophageal infections, often coexisting with other esophageal diseases. About two-thirds of people with AIDS and esophageal candidiasis also have oral candidiasis.[26]

Candidal sepsis is rare.[63] Candida is the fourth most common cause of bloodstream infections among hospital patients in the United States.[64]

History

Descriptions of what sounds like oral thrush go back to the time of Hippocrates circa 460–370 BCE.[17]

Vulvovaginal candidiasis was first described in 1849 by Wilkinson.[65] In 1875, Haussmann demonstrated the causative organism in both vulvovaginal and oral candidiasis is the same.[65]

With the advent of antibiotics following World War II, the rates of candidiasis increased. The rates then decreased in the 1950s following the development of nystatin.[66]

The colloquial term "thrush" refers to the resemblance of the white flecks present in some forms of candidiasis (e.g. pseudomembranous candidiasis) with the breast of the bird of the same name.[67] The term candidosis is largely used in British English, and candidiasis in American English.[65] Candida is also pronounced differently; in American English, the stress is on the "i", whereas in British English the stress is on the first syllable.

The genus Candida and species C. albicans were described by botanist Christine Marie Berkhout in her doctoral thesis at the University of Utrecht in 1923. Over the years, the classification of the genera and species has evolved. Obsolete names for this genus include Mycotorula and Torulopsis. The species has also been known in the past as Monilia albicans and Oidium albicans. The current classification is nomen conservandum, which means the name is authorized for use by the International Botanical Congress (IBC).[68]

The genus Candida includes about 150 different species; however, only a few are known to cause human infections. C. albicans is the most significant pathogenic species. Other species pathogenic in humans include C. tropicalis, C. glabrata, C. krusei, C. parapsilosis, C. dubliniensis, and C. lusitaniae.

The name Candida was proposed by Berkhout. It is from the Latin word toga candida, referring to the white toga (robe) worn by candidates for the Senate of the ancient Roman republic.[65] The specific epithet albicans also comes from Latin, albicare meaning "to whiten".[65] These names refer to the generally white appearance of Candida species when cultured.

Alternative medicine

A 2005 publication noted that "a large pseudoscientific cult"[69] has developed around the topic of Candida, with claims up to one in three people are affected by yeast-related illness, particularly a condition called "Candidiasis hypersensitivity".[70] Some practitioners of alternative medicine have promoted these purported conditions and sold dietary supplements as supposed cures; a number of them have been prosecuted.[71][72] In 1990, alternative health vendor Nature's Way signed an FTC consent agreement not to misrepresent in advertising any self-diagnostic test concerning yeast conditions or to make any unsubstantiated representation concerning any food or supplement's ability to control yeast conditions, with a fine of $30,000 payable to the National Institutes of Health for research in genuine candidiasis.[72]

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