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Candidiasis (Candidosis)

Candida albicans and other Candida species are fungal infections commonly
involved in human disease. Clinical disease may be as varied as
mucocutaneous infections, chronic mucocutaneous candidiasis, candidemia
and sepsis, and invasive infections of internal organs. The mortality rate for
invasive candidal disease is high, estimated to range from 20-40% in children,
particularly preterm infants. Mortality is also high among the elderly,
especially when other comorbid conditions are present.

The increasing incidence of diabetes, malignancy and chemotherapy, and


human immunodeficiency virus and the widespread use of
immunosuppressives and broad-spectrum antibiotics have all contributed to
the rise of Candida infections.
There are over 200 species of the genus Candida; however, only 12 are
associated with significant disease. The most common strain of Candida
involved in cutaneous infection is C. albicans. Other less common strains
include C. tropicalis, C. glabrata, C. parapsilosis, C. stellatoidea, C. krusei, C.
kefyr, and C. dubliniensis.

Candida is a dimorphic fungus (yeast) that colonizes approximately 30% of


healthy individuals. Colonization begins shortly after birth and persists
throughout life. It can be found in the respiratory, gastrointestinal, and
genitourinary tracts and the skin and mucous membranes. Candida exists in
both yeast (blastospore) phase and hyphal (mycelial) phase, depending on
surrounding conditions. Immunocompetent individuals provide effective
immune surveillance against Candida but any immune defect can lead to
infection and visible disease. Transformation of Candida from the yeast phase
to the filamentous form may result in increased virulence due to increased
adhesion to epithelial and endothelial cells.
Characteristic findings on physical examination

Superficial candidiasis can be classified as (1) cutaneous, (2) mucosal


(vulvovaginal, balanopreputial, or oral), (3) paronychial or onychial, or
(4) chronic mucocutaneous candidiasis
• Cutaneous candidiasis
Common sites of involvement include the skin folds (under the
breasts (Figure 1), within the gluteal and inguinal folds, diaper area
(Figure 2), under pannus, and the armpits. Predisposing factors include
heat, humidity, and maceration and patients often complain of burning
and itching. On exam there may be erythema with satellite papules and
overlying white plaques.

Extensive cutaneous
candidiasis in a preterm
infant

Red patches of cutaneous candidiasis in a


submammary location
Oral candidiasis

This presentation is referred to as “thrush.” It can affect people of all


ages but most often occurs in infants and the elderly. Antibiotics,
corticosteroids (oral or inhaled), dental prostheses, chemotherapy,
radiation treatment, and HIV are the most common predisposing
factors.
Pseudomembranous candidiasis presents as whitish plaques on the
oral mucosa. The superficial white component can be wiped off to
reveal an underlying erythematous surface that can bleed easily. This
characteristic differentiates it from leukoplakia, which presents as a
white plaque with irregular borders that is difficult to remove from the
tongue’s surface. Chronic cases of oral thrush can spread to involve the
esophagus.
Diaper dermatitis is the most common dermatologic skin finding in infants
and toddlers. These rashes are episodic in nature and appear on the
protruding surfaces of the buttocks, upper thighs, and lower abdomen.
Atrophic thrush is shiny, atrophic, and can ulcerate. It does not have
overlying white plaques. It is commonly associated with dental prostheses.
Angular cheilitis affects the labial commissures and appears clinically as
erythematous, fissured lesions affecting the corners of the mouth. It can
occur in patients with dentures due to increased saliva drainage along the
corners of the mouth. Skin folds and wrinkling along the labial commissures
can also contribute to this condition due to chronic pooling of saliva. In acne
patients taking isotretinoin, angular cheilitis is common due to cracking at
the corners of the mouth with saliva accumulation.
Median rhomboid glossitis is characterized by an elliptical or
rhomboid-like area on the posterior dorsal tongue, anterior to the
circumvallate papillae.
Mastitis can occur in nearly 20% of breastfeeding women and is
associated with acute erythema and pain on the nipple surface. Risk
factors include a compromised skin surface on the nipple to allow
pathogen entry. Oversupply of breast milk and use of nipple shields can
bring this presentation on.
Vulvovaginal

This presentation can occur at any age but is mainly seen in pregnant
women, those with intrauterine devices, and in women taking oral
contraceptives. Other associations include diabetes, obesity, and
corticosteroid use. It is characterized by erythema of the vulvar and
vaginal mucosa, leucorrhea, and itching.
Balanit

This occurs in uncircumcised or obese men in which the foreskin or


extra skin folds lead to occlusion of the coronal sulcus. It is
characterized by burning, pain, and white sores and secretions along
the glans and foreskin.
Paronychial and onychial

This occurs more commonly on the fingernails, most likely in


individuals who have chronically wet hands such as dishwashers or
laundry workers. Frequent manicures are also a risk factor. Affected
individuals have erythema and tenderness along the proximal and
lateral nail folds. The nail may have a greenish-yellow, ochre, or whitish
discoloration with distal subungual onycholysis.
Chronic mucocutaneous candidiasis

Chronic mucocutaneous candidiasis (CMC) represents a


heterogeneous group of disorders characterized by chronic Candida
infection of the skin, nails, and mucosa. Some of these conditions may
be associated with endocrinopathies as well as decreased cutaneous
immune function, most often due to deficiency of the autoimmune
regulator (AIRE) gene. Unique to CMC is that affected individuals do not
develop invasive candidiasis.
Systemic Implications and Complications

Three components are involved in the pathogenesis of invasive candidiasis:

1. Increased colonization.
2. Breakdown of normal mucosal, skin, or epithelial barrier.
3. Loss of immune mechanisms responsible for preventing candidemia and
invasion to deeper tissues.
Treatment Options

Careful handling of intravenous catheters, careful use of antimicrobial agents, and prompt
removal of infected devices should be performed when possible. Fluconazole prophylaxis has
been used with good results in preventing invasive disease in extremely low birth weight infants.

In cutaneous or mucosal candidiasis, topical antifungal agents are usually adequate. A topical
imidazole (e.g., ketoconazole gel or cream, oxiconazole cream, ketoconazole cream) applied
twice daily is generally effective in treating intertrigo. Ketoconazole should be avoided in the
diaper area due to concerns of systemic absorption.

Nystatin oral suspension (100,000 U/ml - 1 ml swish and spit 4 times a day) or 100,000-unit
pastille for 7-14 days is effective for oral candidal infections. Amphotericin lozenges (10mg) or
suspension (100mg/ml) 4 times a day for 14-21 days is effective as well. Miconazole gel 2% 2.5
ml applied topically 4 times a day for 14-21 days is also a treatment option.
For paronychia and onychia, systemic treatment should be used. Effective
regimens include: itraconazole 200 mg daily for 3 months or 200 mg BID for 1
week each month for 3 months and fluconazole 150-300 mg weekly in adults
or 1-2 mg/kg weekly in children for 4-6 weeks. Topical treatments with
topical azoles, such as efinaconazole and tavaborole, can be attempted in
children and adults who cannot take systemic antifungals.

Chronic systemic antifungals are used in the prevention and treatment of


CMC. Antifungal sensitivity studies are helpful in directing therapy. Adjunct
therapy with calcium channel blockers can overcome resistance to
antifungals through a synergistic effect.

Empiric therapy should be considered for patients known to be neutropenic


to reduce risk of invasive candidiasis. For patients with candidemia,
echinocandins (caspofungin loading dose 70 mg, then 50 mg daily;
anidulafungin loading dose 200 mg, then 100 mg daily; micafungin 100 mg
daily) may be more effective than fluconazole or amphotericin B.
Lipid formulation amphotericin B (3-5 mg/kg daily) is an alternative if
there is resistance to a more desired medication or lack of availability
of other therapies. Transition to fluconazole should be done promptly
within 5-7 days if the strain is susceptible or repeat cultures are
negative, as there is significant toxicity with using amphotericin B.

Probiotics have been shown to suppress candidal growth in oral,


vaginal, and enteric cavities, as well as biofilm development. As such,
they can be included in the treatment regimen against chronic
colonization.

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