Cutaneous Candidiasis 

Updated: May 22, 2018
Author: Noah S Scheinfeld, JD, MD, FAAD; Chief Editor: Dirk M Elston, MD 

Overview

Background

Cutaneous candidiasis and other forms of candidosis are infections caused by the yeast Candida albicans or other Candida species. Yeasts are unicellular fungi that typically reproduce by budding, a process that entails a progeny pinching off of the mother cell. C albicans, the principal infectious agent in human infection, is an oval yeast 2-6 µm in diameter. C albicans (as well as most medically significant fungi) has the ability to exist in both hyphal and yeast forms (termed dimorphism). If pinched cells do not separate, a chain of cells is produced and is termed pseudohyphae.

Superficial infections of skin and mucous membranes are the most common types of candidal infections of the skin. Common types of candidal skin infection include intertrigo, diaper dermatitis, erosio interdigitalis blastomycetica, perianal dermatitis, and candidal balanitis. In certain subpopulations, candidal infection of the skin has increased in prevalence in recent years, principally because of the increased numbers of patients who are immunocompromised.

Esophagitis, septicemia, endocarditis, peritonitis, and urinary tract infections are less frequent types of candidosis. Although C albicans is the most common cause of human infection, the genus Candida includes more than 150 species. Candida tropicalis, Candida parapsilosis, Candida guilliermondi, Candida krusei, Candida kefyr, Candida zeylanoides, and Candida glabrata (formerly Torulopsis glabrata) are less common causes of human disease.

Humans carry yeast fungi, including candidal species, throughout the gastrointestinal tract (mouth through anus) as part of the normal commensal flora. The vagina also commonly is colonized by yeast (13% of women), most commonly by C albicans and C glabrata. The commensal oral isolation of candidal species ranges from 30-60% in healthy adults. Note that Candida species are not part of the normal flora of the skin; however, they may colonize fingers or body folds transiently.

Also see the articles Mucosal Candidiasis and Candidiasis.

Pathophysiology

Most candidal species are known to produce virulence factors including protease factors. Those strains lacking virulence factors have been shown to be less pathogenic. The ability of yeast forms to adhere to the underlying epithelium is an important step in the production of hyphae and tissue penetration. Removal of bacteria from the skin, mouth, and gastrointestinal tract by exposing to tissue with its endogenous flora results in inhibition of endogenous microflora, providing reduced environmental and nutritional competition that favors the growth of candidal organisms.

Additional research has been performed on the cytokines and interleukins that candidal organisms affect in keratinocytes. In keratinocytes, C albicans phospholipomannan triggers an inflammatory response through toll-like receptor 2.[1] C albicans aborts the expression of interferon-gamma–inducible protein-10 in human keratinocytes.[2] These factors probably explain how candidal infections occur in the skin, which has innate defenses against candidal organisms.

A 2013 review of pathologic mechanisms of C albicans cited (1) the secretion of hydrolases, (2) molecules that mediate adhesion to with concomitant invasion into host cells, (3) the yeast-to-hypha transition, (4) biofilm formation, (5) contact sensing and thigmotropism, (6) phenotypic switching, and (7) a variety of fitness attributes.[3]

Genetic conditions can make the skin susceptible to candidal infection. One such condition is autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED),[4] which manifests with at least 2 of 3 conditions: Addison disease, chronic mucocutaneous candidiasis, or hypoparathyroidism, called the Whitaker triad or referred to as polyglandular autoimmune syndrome type 1 (PAS-1) or APECED.[5] . It is related to autoimmune regulator (AIRE) genetic mutations.[6]

STAT1 gain-of-function mutations can cause chronic mucocutaneous candidiasis, while STAT3 loss-of-function mutations cause the autosomal dominant hyper-IgE syndrome associated with mucocutaneous candidiasis.[7, 8]

Mucocutaneous candidiasis, can occur in interleukin (IL)–12 receptor β1 deficiency and can be the presenting sign of such a deficiency.[9]

In APECED patients, autoantibodies to IL-17A can be linked to mucocutaneous candidiasis severity.[10]

IL-17 is an essential interleukin in combatting C albicans infections.[11, 12, 13] Thus, phenotypes that knock out 1L-17 are more susceptible to C albicans and drugs such as secukinumab, an IL-17 blocker for psoriasis, can increase the incidence of candidal infections.

Etiology

Host factors that predispose patients to infections are numerous. Local factors such as tissue damage resulting from trauma, xerostomia, radiation-induced mucositis, ulcerations, skin maceration, or occlusion enhances adhesion and predisposes patients to increased infection rates.

Endocrine diseases such as diabetes mellitus, Cushing syndrome, hypoparathyroidism, hypothyroidism, and polyendocrinopathy are associated with increased susceptibility to infection. The mechanism by which diabetes mellitus is believed to raise infection rates is through increased tissue glucose, altered yeast adhesion, and decreased phagocytosis.

Nutritional deficiencies may alter host defense mechanisms or epithelial barrier integrity, allowing increased adherence or penetration. Iron deficiency anemia and deficiencies including vitamins B1, B2, B6, C, and folic acid are associated with heightened infection rates.

T-lymphocyte–mediated immunity plays an important immunologic role against infection through phagocytosis and killing by polymorphonuclear cells and macrophages. Individuals with deficient T-lymphocyte function, such as patients with AIDS, appear to be particularly vulnerable to mucosal or cutaneous candidiasis but not to systemic infection. Patients with primary immune deficiencies, such as lymphocytic abnormalities, phagocytic dysfunction, IgA deficiency, viral-induced immune paralysis, and severe congenital immunodeficiencies, often are affected by oropharyngeal candidiasis and other fungal mycoses.

Epidemiology

Frequency

United States

Candida species are a common cause of intertrigo in both elderly and diabetic patients. Candida species currently are the fourth leading cause of bloodstream infections in the United States, with occurrence at a disproportionately high rate in persons aged 65 years and older.

International

A German study[14] investigated the different causes of diaper dermatitis in 46 men and women at a median age of 85 years. In 38 patients, a cause was established; specifically, 63% had candidiasis, 16% had irritant dermatitis, 11% had eczema, and 11% had psoriasis. Of these patients, 37 were treated and 73% were cured after 8 weeks of treatment.

In Germany, Krãnke et al[15] studied 126 patients with a presumptive diagnosis of anal eczema (age range, 7-82 y), and most patients were male (57.1% male, 42.9% female). The clinical diagnosis was intertrigo/candidiasis in 42.9% of patients.

In Argentina, Nardin et al[16] analyzed 2073 samples of skin, hair, nails, and oral mucous membranes obtained from 1817 patients who attended the Microbiology Branch of the Central Laboratory at Dr. J.M. Cullen Hospital from September 1999 to September 2003. The samples were examined and identified according to localization and the type of lesion. Of the total samples, 55.67% were positive; 63% were recovered from females and 37% were recovered from males. C albicans was the prevalent yeast species.

In Japan, Nishimoto[17] noted that cutaneous candidiasis was seen in 755 (1%) of 72,660 outpatients. Intertrigo (347 cases) was the most common clinical manifestation of cutaneous candidiasis, erosio interdigitalis occurred in 103 cases, and diaper candidiasis was noted in 102 cases.

A Spanish study of 3,097 inpatient cases noted that cutaneous candidiasis accounted for 7.1% of consultations.[18]

Age

Neonatal cutaneous and systemic candidiasis have become increasingly prevalent in neonatal intensive care nurseries. Postnatal acquisition has been attributed to increased survival rates of low birth weight babies in association with an increased number of invasive procedures and widespread use of broad-spectrum antibiotics. Neonatal candidiasis presents 3-7 days after birth with oral thrush and diaper dermatitis. This has been attributed to mucosal contact with the organism during labor and delivery.

An interesting case from Spain was noted in 2012, in which a mother had subclinical vaginal candidal infection and passed the infection to her full-term infant, who developed the disease 24 hours after being born.[19] Sepsis, respiratory distress, and a positive culture in the blood for Staphylococcus aureus ensued. Biopsy proved Candida was the provoking agent; the patient survived.

The number of candidal infections has risen dramatically in recent years, mirroring the increasing number of patients who are immunocompromised. Specifically, increased age appears to be associated with increased morbidity and mortality. Older adults are more likely to be exposed to situations that increase the risk of invasive candidiasis, including treatment with broad-spectrum antibiotics, hyperalimentation, and increased contact with invasive monitoring devices in an intensive care unit. Superficial candidal infections, although typically believed to be benign, cause significant morbidity in the elderly population.

Candidal infections are exacerbated by certain types of medication (eg, antibiotics), poor self-care, and decreased salivary flow, all of which often are associated with aging. In addition, treatment with cytotoxic agents (eg, methotrexate, cyclophosphamide) for dermatologic and rheumatic conditions or aggressive chemotherapy for malignancy in elderly patients puts them at higher risk.

Prognosis

Superficial candidal infections cause significant morbidity in older adults, which becomes a particular problem with the use of certain types of medication, poor self-care, and decreased salivary flow. Age alone is not sufficient for the development of candidal infection; however, increased morbidity is associated with both superficial and invasive forms of disease. This is a result of an increased risk in patients of developing an underlying immunosuppressed state, such as malignancy.

Patient Education

For patient education resources, see the Yeast and Fungal Infections Center and Children's Health Center, as well as Candidiasis (Yeast Infection), Yeast Infection Diaper Rash, and Yeast Infection Skin Rash.

 

Presentation

History

Candidal vulvovaginitis

This common condition in women presents with itching, soreness, and a thick creamy white discharge (see the image below).

A moist, erosive, pruritic patch of the perianal s A moist, erosive, pruritic patch of the perianal skin and perineum (with satellite pustule formation) is demonstrated in this woman with extensive candidosis.

Although most candidal infections occur more frequently with advancing age, vulvovaginitis is unusual in older women. In the absence of estrogen stimulation, the vaginal mucosa becomes thin and atrophic, producing less glycogen. Candidal colonization of vaginal mucosa is estrogen dependent and subsequently decreases sharply after menopause (see the image below).

Discrete superficial pustules developed within hou Discrete superficial pustules developed within hours of birth on the hand of an otherwise healthy newborn. A potassium hydroxide preparation revealed spores and pseudomycelium, and culture demonstrated the presence of Candida albicans.

In contrast, the likelihood of colonization increases during pregnancy (25-33%). The widespread use of hormone replacement for reduction of osteoporosis and heart disease may cause an increasing trend in candidal vulvovaginitis among older women. Cutaneous hypersensitivity to C albicans has been reported in persons with idiopathic vulvodynia.[20]

Candidal balanitis

Signs and symptoms of this candidal infection vary but may include tiny papules, pustules, vesicles, or persistent ulcerations on the glans penis (see the image below). Exacerbations following intercourse are common.

Dry, red, superficially scaly, pruritic macules an Dry, red, superficially scaly, pruritic macules and patches on the penis represent candidal balanitis.

Congenital candidosis[21, 22]

This rarely reported candidal infection (70 cases during the 1990s) may be acquired by the infant in utero or during delivery. Presumably, congenital candidosis is an ascending intrauterine infection with cutaneous or systemic manifestations that typically present within 12 hours after birth. Although the congenital systemic form typically is fatal, congenital cutaneous infections usually have a more benign course. Prematurity and the presence of an intrauterine foreign body (intrauterine device) are associated with this condition. Untreated, infants are at higher risk for systemic infection, which is associated with a high mortality rate (70%). Some infants have respiratory distress and pneumonia secondary to in utero aspiration of infected amniotic fluid.

Oropharyngeal candidiasis[23]

This form is known more commonly as oral thrush and is considered by many to be a minor problem of little significance that may clear spontaneously. However, without appropriate treatment this can lead to a chronic condition that can result in discomfort and anorexia. Rarely, oropharyngeal infection leads to systemic candidiasis.

Oropharyngeal candidiasis in the neonate most commonly is acquired from the infected maternal mucosa during passage of the infant through the birth canal. Oropharyngeal candidiasis is 35 times more common in neonates of infected mothers compared to uninfected mothers.

Oropharyngeal candidiasis is the most common type of clinical presentation in infants and children. Immaturity of host defenses and incomplete establishment of the normal orointestinal flora are likely reasons why C albicans often acts as a pathogen in the neonate compared to a child aged several months who is not nearly as susceptible. Beyond the neonatal age, C albicans is considered a normal constituent of the oral and intestinal florae.

Candidosis of the nipple in the nursing mother is associated with infantile oropharyngeal candidiasis. Nipple candidosis almost always is bilateral, with the nipples appearing bright red and inflamed, with the look and feel of being sunburned or on fire. Unlike a painful-with-nursing cut or abrasion from local trauma by the infant (incorrect latch-on), nipple candidosis hurts between feedings. Merely having the clothing brush against the nipples is painful.

Candidal diaper dermatitis[23]

Infants with oropharyngeal candidiasis invariably harbor C albicans in the intestine and feces (85-90%). In most patients, candidal diaper dermatitis is the result of progressive colonization from oral and gastrointestinal candidiasis. Infected stools represent the most important focus for cutaneous infection. Moist macerated skin is particularly susceptible to invasion by C albicans. Additional factors that predispose infants to candidal diaper dermatitis include local irritation of the skin by friction; ammonia from bacterial breakdown of urea, intestinal enzymes, and stool; detergents; and disinfectants.

Diaper dermatitis candidiasis can result in an a generalized eruption known as an Id reaction, also known as autosensitization or an autoeczematization reaction.[24]

Oral candidiasis in adults

Use of broad-spectrum antibiotics and inhaled corticosteroids, diminished cell-mediated immunity, and xerostomia are all risk factors for candidiasis (see the image below).

White plaques are present on the buccal mucosa and White plaques are present on the buccal mucosa and the undersurface of the tongue and represent thrush. When wiped off, the plaques leave red erosive areas.

Xerostomia may be either primary resulting from the natural aging process or secondary resulting from the anticholinergic effect of certain drugs including psychoactive drugs such as phenothiazines and tricyclic antidepressants. A decrease in salivary production decreases both the amount of available mucosal secretory antibody (immunoglobulin A [IgA]) and the natural cleansing action provided by saliva.

In older adults, the development of oral thrush in the absence of a known etiology should raise the clinician's index of suspicion for an underlying cause of immunosuppression, such as malignancy or AIDS. Superficial mycoses may be the presenting sign in immunodepressed patients (especially AIDS).[25]

With denture stomatitis, the areas of erythema may be painful and may affect up to 65% of patients who wear dentures, especially those who wear full sets. Despite popular belief, denture stomatitis is not associated with smokers or patients who are immunosuppressed.

Intertrigo

Most cases of cutaneous candidosis occur in skin folds where occlusion (by clothing or shoes) produces abnormally moist conditions. Sites such as the perineum, mouth, and anus, in which Candida organisms normally may be carried, are at further risk of infection. Candidal infection of the skin under the breasts or pannus occurs when those areas become macerated (see the image below).

Erythema, maceration, and satellite pustules in th Erythema, maceration, and satellite pustules in the axilla, accompanied by soreness and pruritus result in a form of intertrigo.

Decubital candidosis

This is a particular form of cutaneous candidosis that occurs on the dorsal skin of chronically bedridden patients.[26]

Paronychia

Candida organisms occasionally cause infection in the periungual area and underneath the nailbed (see the image below). Candida species (not always C albicans) can be isolated from most patients with chronic paronychia. The yeast is believed to play an etiologic role in this condition, but bacteria also may act as co-pathogens. Immediate contact dermatitis to food allergens may play a role in the pathogenesis of the condition as well. Progression to total nail dystrophy has been associated specifically with C albicans and usually has been limited to women with 2 important predisposing conditions, ie, Cushing syndrome and Raynaud disease. Disease is more common in people who frequently submerge their hands in water and usually is not associated with the elderly population. One important exception to this generalization is the population of patients with diabetes.

A nailfold with candidal infection becomes erythem A nailfold with candidal infection becomes erythematous, swollen, and tender with an occasional discharge

Candidosis and HIV

Epidemiologic studies indicate that a very high percentage of patients infected with HIV contract some type of skin disorder during the course of the disease.[27, 28, 29] More specifically, most patients with HIV infection have some form of candidal infection during the illness. Recurrent episodes of oral candidiasis typically occur in patients in whom CD4 counts are less than 300/µL, an important marker of disease progression. Additionally, Yanagisawa et al,[30] in 2007, reported on a case of disseminated candidiasis as an initial presentation of AIDS. Such cases often manifest with purpuric eruptions.

Breast pain

Andrews et al[31] studied 98 breastfeeding women, 20 who reported breastfeeding associated pain and 78 who were asymptomatic. Cultures were obtained from breast milk, areolae, and the infants' oropharynx. Six of the 20 symptomatic women returned breast milk cultures positive for yeast, compared with 6 of 78 controls (11 of 12 samples showed C albicans). The researchers suggested that Candida might play an etiologic role in breastfeeding-associated pain.

Ecthyma gangrenosum

In 2007, Agarwal et al[32] reported on a solitary ecthyma gangrenosum–like lesion that resulted from C albicans infection in a neonate.

Ulcers

Xi et al,[33] in 2007, reported a 51-year-old Cantonese woman who had a 1-year history of a large, deep-seated subcutaneous ulcer on her right shoulder for more than a year whose discharge showed C albicans and C parapsilosis. The researchers isolated C parapsilosis from the biopsy specimen.

Cutaneous candidiasis has manifested as an interdigital ulcer.[34]

Other

Cutaneous candidiasis was noted to occur under a ruby ring in a patient who was immunocompromised.[35]

Generalized cutaneous candidiasis can complicate Darier disease.[36]

Physical Examination

Candidal vulvovaginitis

Clinical examination reveals erythema of the vaginal mucosa and vulval skin with curdy white flecks within the discharge. Erythema may spread to include the perineum and groin, with satellite pustules. Alternatively, the vaginal mucosa may appear red and glazed. A patient presenting with symptoms of vulvovaginitis with identification of yeasts in the vaginal discharge has a diagnosis of candidosis.

Congenital candidosis

In 2004, Diana et al[37] reported that cutaneous congenital candidiasis is a rare disease of term or premature infants. It typically manifests as an erythematous maculopapular eruption affecting the trunk and extremities; it resolves after extensive desquamation. Pustules and vesicles usually are superficial and resolve spontaneously or with topical treatment (see the image below). The presence of white microabscesses on the placenta and umbilical cord of an infant with such an eruption must suggest the diagnosis of cutaneous congenital candidiasis. It is always secondary to candidal chorioamnionitis, but it may pass unrecognized.

Fine superficial pustules on an erythematous patch Fine superficial pustules on an erythematous patchy base are suggestive of candidosis.

Oropharyngeal candidiasis in the infant

Lesions become visible as pearly white patches on the mucosal surfaces. Buccal epithelium, gums, and the palate commonly are involved with extension to the tongue, pharynx, or esophagus in more severe cases. If the lesions are scraped away, an erythematous base is exposed. Lesions may progress to symptomatic erosion and ulceration.

Candidal diaper dermatitis

The eruption of candidal diaper dermatitis usually starts in the perianal area, spreading to involve the perineum and, in severe cases, the upper thighs, lower abdomen, and lower back. Maceration of the anal mucosa and the perianal skin often is the first clinical manifestation. The typical eruption begins with scaly papules that merge to form well-defined, weeping, eroded lesions with a scalloped border. A collar of overhanging scales and an erythematous base may be demonstrated. Satellite flaccid vesicopustules around the primary intertriginous plaque also are characteristic of candidal diaper dermatitis and represent the primary lesions. Candidiasis may be a presenting feature of diabetic ketoacidosis.[38]

Oral candidiasis in elderly persons

The most common clinical appearance of oropharyngeal candidiasis (pseudomembranous candidosis or oral thrush) in the adult population occurs as white plaques that are present on the buccal, palatal, or oropharyngeal mucosa overlying areas of mucosal erythema. Typically, the lesions are removed easily and may demonstrate areas with tiny ulcerations (see the image below). In addition, some patients may develop soreness and cracks at the lateral angles of the mouth (angular cheilitis). Denture stomatitis presents as chronic mucosal erythema typically beneath the site of a denture.

Soreness and cracks at the lateral angles of the m Soreness and cracks at the lateral angles of the mouth (angular cheilitis) is a frequent expression of candidosis in elderly individuals.

Intertrigo

Intertrigo typically presents with erythema, cracking, and maceration with soreness and pruritic symptoms. Lesions typically have an irregular margin with surrounding satellite papules and pustules. Web spaces of affected fingers or toes are macerated and have the appearance of soft white skin, which is a condition termed erosio interdigitalis blastomycetica (interdigital candidosis).

Paronychia

The nailfold becomes erythematous, swollen, and tender, with an occasional discharge. Loss of the cuticle occurs, along with nail dystrophy and onycholysis with discoloration around the lateral nailfold (see the image below). A greenish color with hyponychial fluid accumulation may occur that results entirely from Candida, and not Pseudomonas, infection. A potassium hydroxide (KOH) preparation is helpful and is likely to show yeast organisms.

Candida infection should be in the differential di Candida infection should be in the differential diagnosis when one or more nails become discolored, has subungual discoloration, nailplate separation from the nailbed, and lack evidence of a dermatophyte.
 

DDx

Diagnostic Considerations

Also consider the following:

  • Bacterial vaginosis
  • Contact dermatitis with or without colonization
  • Pseudomonas nailbed infection
  • Inverse psoriasis
  • Radiation dermatitis
  • Trichomonas infection

Duong et al[39] noted 2 cases of extensive cutaneous candidiasis complicating cutaneous T-cell lymphoma. Be aware that cutaneous T-cell lymphoma may underlie extensive candidiasis.

Differential Diagnoses

 

Workup

Laboratory Studies

KOH preparation is the easiest and most cost-effective method for diagnosing cutaneous congenital candidiasis, but its use is not sufficient in the absence of other supporting clinical evidence.

Culture from an intact pustule, skin biopsy tissue, or desquamated skin can help to support the diagnosis.

Microscopic examination of skin scrapings prepared with calcofluor white stain is a simple way of detecting yeasts and pseudohyphae of Candida albicans. C albicans binds nonspecifically to polysaccharides found in fungal cell walls and produces a distinct bright color in a pattern characteristic for the organism when viewed under a fluorescence microscope.

When a greenish hyponychial fluid accumulates, material may be obtained by heating a pin and painlessly puncturing the intact overlying nail. The fluid release provides symptomatic relief to the patient, and fluid may demonstrate multiple yeast organisms when viewed using KOH preparation.

Lim and Lim report on a new contrast stain, trypan blue, for rapid diagnosis of candidal dermatomycoses.[40]

Histologic Findings

A skin biopsy specimen stained with a periodic acid-Schiff stain reveals nonseptated hyphae. The presence of nonseptated hyphae allows cutaneous candidiasis to be distinguished from tinea.

Of all the types of Candida, the electron microscope shows that C albicans is the most confluent in its adherence to the skin.[41]

 

Treatment

Medical Care

Candidal vulvovaginitis

Topical antifungal agents including miconazole nitrate (Micatin, Monistat-Derm) or clotrimazole (Lotrimin, Mycelex) creams are curative. One-time oral therapy with fluconazole (150 mg) or itraconazole (600 mg) is effective and may be a more attractive alternative to some patients, but it is more costly.

Candidal balanitis

Topical therapy is sufficient in most patients. Evaluate asymptomatic sexual partners and treat them if they are affected. If persistent lesions spread beyond the genitalia, consider the possibility of diabetes, and assess for the disease.

Congenital candidosis

Topical preparations usually are effective. Some authors recommend the use of oral nystatin in conjunction with topical agents to lower the risk of systemic infection.

Oropharyngeal candidiasis in the infant

Most patients can be treated with nystatin oral suspension. Treat for 10-14 days or until 48-72 hours after resolution of symptoms. Dosage for preterm infants is 0.5 mL (50,000 U) to each side of mouth 4 times/day; dosage for infants is 1 mL (100,000 U) to each side of the mouth 4 times/d.

Candidosis of the nipple

Treat nipple candidosis for 2 weeks using an antifungal cream after each feeding. The baby must be treated simultaneously with nystatin swabbed on all 4 gum lines and in the oral cavity, along with a few ingested drops, for 2 weeks. Babies may have no symptoms of oropharyngeal candidiasis and still be reinfecting their mothers. Careful hygiene is also important. Frequent changing and washing of bras in boiling water (along with anything the baby puts in its mouth, eg, pacifiers) is necessary. Gentian violet is not used because it stains badly and may irritate the infant's mouth. If candidosis of the nipple goes untreated, it may extend, and oral treatment for the mother may be necessary. Cultures often are not pure and usually are not helpful.

Candidal diaper dermatitis

Treatment for candidal diaper dermatitis includes practical measures that reduce the amount of time the diaper area is exposed to hot and humid conditions. Air drying, frequent diaper changes, and generous use of baby powders and zinc oxide paste are adequate preventive measures. For topical therapy of candidal diaper dermatitis, nystatin, amphotericin B, miconazole, and clotrimazole are effective and almost equivalent in efficacy.

Oral candidiasis in adults

Treatment with a topical agent such as nystatin (1:100,000 U/mL, 5 mL oral rinse and swallow qid) or clotrimazole troches (10 mg 5 times/d) usually is effective. In most patients, extend the duration of antifungal therapy at least twice as long as the termination of clinical signs and symptoms of candidosis. Reserve oral fluconazole, 100 mg once daily for 2 weeks, for patients with more severe disease.

With denture stomatitis, improved oral hygiene with removal of dentures at night, vigorous brushing to remove plaque, and disinfecting (swish and spit) with chlorhexidine gluconate (Peridex) usually is adequate treatment. Topical therapy with clotrimazole troches or nystatin may be used for lesions that do not respond to the above measures. For more resistant cases oral fluconazole, 100 mg/day for several weeks, in addition to the above measures, may prove effective.

Intertrigo

Treatment is targeted to keeping the skin dry, with the addition of topical nystatin powder, clotrimazole, or miconazole twice daily, often in conjunction with a midpotency corticosteroid. Patients with extensive infection may require the addition of fluconazole (100 mg PO qd for 1-2 wk) or itraconazole (100 mg PO qd for 1-2 wk). Many anecdotally based remedies exist for intertrigo that have been used in dermatology offices for years with success. The remedies have focused on both drying the moist inflamed area and treating the candidosis. The treatments are adjusted based on whether the inflammation is acute (wet and red), subacute (red +/- maceration), or chronic (red and dry)

For acute intertrigo, Domeboro solution, Castellani paint, or vinegar/water (1 tbsp vinegar per qt room-temperature water) may be applied twice per day for 5-10 minutes for 3-5 days as needed. Dry the area with a hair dryer (no heat). Apply a shake lotion twice per day (mixture: 40 g USP talc, 40 g zinc oxide, 10 g glycerin; mix into slurry or milkshake consistency, add distilled water up to 120 mL, dispense in 180-mL [6 oz] bottle). Place a large bath towel under breasts or in pendulous areas twice per day. Castellani paint (carbol fuchsin) is messy, but nightly painting may help when nothing else does. Some patients respond well to triamcinolone-nystatin cream.

For subacute intertrigo, benzoyl peroxide wash may be used to cleanse the area instead of application of vinegar or Castellani paint. A topical anticandidal cream of choice is applied twice per day, with or without a mild hydrocortisone cream (no refills for the latter).

For chronic intertrigo, the zinc-talc shake lotion may be used once or twice daily, and the hydrocortisone cream/antifungal mixture may be applied at night. Local hyperhidrosis may be treated with antiperspirants (ie, Arrid Extra Dry Unscented, Dry Idea) on a long-term basis. These products, along with the more concentrated Drysol (aluminum chloride 20%), may sting macerated skin. Nystatin in talc (100,000 U/g or 15 g) may be applied twice per day for a few days, then tapered and replaced with unscented baby powder as a powder-approach alternative.

Sundaram et al[42] noted that candidal intertrigo can be treated with filter paper soaked in Castellani paint.

Paronychia

Treatment with topical agents usually is not effective but should be tried for chronic candidal paronychia. Drying solutions or antifungal solutions are used. Oral therapy with either itraconazole (pulse dosing with 200 mg bid for 1 wk of each of 3 consecutive mo) or terbinafine (250 mg qd for 3 mo) is recommended.

Candidosis and HIV

Topical therapy with agents such as nystatin and clotrimazole require a minimum of 20-30 minutes of drug contact with the oral mucosa. Treatment with topical therapies may be effective in the early stages of HIV infection, and it becomes less effective with disease progression. Oral treatment with a 2-week course of antifungal therapy (itraconazole, fluconazole, ketoconazole) is indicated in more refractory cases. In patients who are significantly immunocompromised, maintenance therapy on an intermittent (alternate days to twice weekly dosing of ketoconazole 200 mg or fluconazole 100 mg) or continuous basis may be required to provide symptomatic relief. In general, the goal is the cessation of therapy once clinical symptoms have subsided, since prolonged therapy increases the likelihood of the development of drug-resistant organisms.

Guidelines

Related clinical guidelines have been released by the Infectious Diseases Society of America.[43] See Clinical Practice Guideline for the Management of Candidiasis: 2016 Update by the Infectious Diseases Society of America.

 

Medication

Medication Summary

The azoles are a group of synthetic antimycotic agents with a broad spectrum of activity. The primary drugs available include ketoconazole, miconazole, fluconazole, itraconazole, and econazole. The mechanism of action of azoles is blocking the synthesis of ergosterol, the primary sterol in the fungal cell membrane. The depletion of ergosterol alters the fluidity of the cell membrane and alters the action of the membrane-associated enzymes. This results in inhibition of replication and inhibition of the transformation of candidal yeast forms into hyphae, which is the invasive and pathogenic form of the parasite.

Nystatin and amphotericin are polyenes, which are active against some fungi but have little action on mammalian cells and no action on bacteria. They bind to cell membranes and interfere with permeability and transport functions. These antibiotics act as ionophores and causes leakage of cations.

Terbinafine is an allylamine that is fungicidal for a wide range of skin pathogens. It inhibits squalene epoxidase, which is involved in the synthesis of ergosterol from squalene in the fungal cell wall. The accumulation of squalene within the cell is toxic to the organism.

Naftifine (an allylamine antifungal) 2% cream, which is a stronger version of the older 1% cream, is a promising agent for hard-to-treat cutaneous candidal infections.[44]

A case of chronic mucocutaneous candidosis that was cured with micafungin has been reported.

Voriconazole is another third-line treatment.

A stable nitric oxide (NO)–releasing nanoparticle (NO-np) system for treating cutaneous candidiasis has been proposed as a new treatment for extensive cutaneous candidiasis in burn patients.[45]

Essential oils are potential causes of allergic contact dermatitis, but may play an evolving role in the treatment of azole-resistant cutaneous infections.[46]

Antifungal agents

Class Summary

Antifungal agents exert their fungicidal effect by altering the permeability of fungal cell membranes. The mechanism of action also may involve an alteration of RNA and DNA metabolism or an intracellular accumulation of peroxide toxic to the fungal cell.

Nystatin (Mycostatin)

Nystatin is a fungicidal and fungistatic antibiotic obtained from Streptomyces noursei. It is effective against various yeasts and yeastlike fungi. Nystatin changes permeability of the fungal cell membrane after binding to cell membrane sterols, causing cellular contents to leak.

Treatment should continue until 48 hours after the disappearance of symptoms.

Miconazole topical (Micatin, Monistat-Derm, Monistat)

Miconazole damages the fungal cell wall membrane by inhibiting the biosynthesis of ergosterol. Membrane permeability is increased, causing nutrients to leak out, resulting in fungal-cell death.

Lotion is preferred in intertriginous areas. If cream is used, apply sparingly to avoid maceration effects.

Clotrimazole (Lotrimin, Mycelex, Gyne-Lotrimin)

Clotrimazole is a broad-spectrum antifungal agent that inhibits yeast growth by altering cell membrane permeability, causing death of fungal cells. Reevaluate the diagnosis if no clinical improvement is seen after 4 weeks.

Fluconazole (Diflucan)

Fluconazole is a synthetic oral antifungal (broad-spectrum bistriazole) that selectively inhibits fungal cytochrome P-450 and sterol C-14 alpha-demethylation.

Itraconazole (Sporanox)

Itraconazole is a synthetic triazole antifungal agent that slows fungal cell growth by inhibiting cytochrome P-450–dependent synthesis of ergosterol, a vital component of fungal cell membranes.

Terbinafine (Lamisil)

Terbinafine is used for the treatment of paronychia; it is an allylamine antifungal, which inhibits squalene epoxidase and decreases ergosterol synthesis, causing fungal-cell death.

Use the medication until symptoms significantly improve. The duration of treatment should be longer than 1 week but not longer than 4 weeks. Terbinafine may not be as effective for candidal infections as azole antifungals.

 

Questions & Answers

Overview

What is cutaneous candidiasis?

What is the pathophysiology of cutaneous candidiasis?

What is the role of genetics in the pathophysiology of cutaneous candidiasis?

What causes cutaneous candidiasis?

What is the prevalence of cutaneous candidiasis in the US?

What is the global prevalence of cutaneous candidiasis?

Which patient groups are at highest risk for cutaneous candidiasis?

What is the prognosis of cutaneous candidiasis?

Where can patient education resources for cutaneous candidiasis be found?

Presentation

Which clinical history findings are characteristic of candidal vulvovaginitis?

What are the signs and symptoms of candidal balanitis?

What are the risk factors for congenital candidiasis?

Which clinical history findings are characteristic of oropharyngeal candidiasis (oral thrush)?

Which clinical history findings are characteristic of candidal diaper dermatitis?

What are the risk factors for oral candidiasis in adults?

What are common sites for intertrigo in patients with cutaneous candidiasis?

What is decubital candidosis?

Which history findings are characteristic of paronychia in patients with cutaneous candidiasis?

What is the prevalence of cutaneous candidiasis in patients with HIV?

What is the role of candidiasis in breastfeeding-associated pain?

What are rare presentations of cutaneous candidiasis?

Which physical findings are characteristic of candidal vulvovaginitis?

Which physical findings are characteristic of congenital candidosis?

Which physical findings are characteristic of oropharyngeal candidiasis in infants?

Which physical findings are characteristic of candidal diaper dermatitis?

Which physical findings are characteristic of oral candidiasis in elderly persons?

Which physical findings are characteristic of intertrigo?

Which physical findings are characteristic of paronychia?

DDX

Which conditions should be included in the differential diagnoses of cutaneous candidiasis?

What are the differential diagnoses for Cutaneous Candidiasis?

Workup

What is the role of lab studies in the workup of cutaneous candidiasis?

Which histologic findings are characteristic of cutaneous candidiasis?

Treatment

What are the treatment options for candidal vulvovaginitis?

What is included in the treatment of candidal balanitis?

What is included in the treatment of congenital candidosis?

How is oropharyngeal candidiasis treated in infants?

What is included in the treatment of candidosis of the nipple?

What are the treatment options for candidal diaper dermatitis?

What are the treatment options for oral candidiasis in adults?

What are the treatment options for intertrigo?

What are the treatment options for paronychia?

What are the treatment options for cutaneous candidiasis in patients with HIV infection?

What guidelines have been published for the management of cutaneous candidiasis?

Medications

Which medications are used in the treatment of cutaneous candidiasis?

Which medications in the drug class Antifungal agents are used in the treatment of Cutaneous Candidiasis?