Cutaneous Candidiasis

Updated: Feb 05, 2016
  • Author: Noah S Scheinfeld, JD, MD, FAAD; Chief Editor: Dirk M Elston, MD  more...
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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.

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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]

Mucocutaneous candidiasis, can occur in interleukin (IL)–12 receptor β1 deficiency and can be the presenting sign of such a deficiency. [7]

In APECED patients, autoantibodies to IL-17A can be linked to mucocutaneous candidiasis severity. [8]

IL-17 is an essential interleukin in combatting C albicans infections. [9, 10, 11] 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.

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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 [12] 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 [13] 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 [14] 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 [15] 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. [16]

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. [17] 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.

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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.

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