fungal infections part ii

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• Etymology: Latin, feminine ofCandidus= /Clear.

• Candidal infection is known as ‘candidiasis’, ‘candidosis’ or older name ‘moniliasis’.

• Mucocutaneous candidiasis is mostcommonly due to C. albicans, followed by C. tropicalis.

• Candida are unicellular yeast-like fungi that typically reproduce by budding, a process that entails pinching off of the mother cell.

• It has the ability to exist in both yeast and hyphal forms (dimorphism).

• Pseudohyphae are yeast cells that have elongated and remained attached to each other and they have constricted the ends.

• Candidal species are part of the normal commensal florathroughout the gastrointestinal tract (mouth through anus).

• The vagina also is commonly colonized by yeast (13% of women), most commonly by C. albicans.

1. Infancy: Postnatal acquisition has been attributed to increased survival rates of low birth weight babies in association with an increased number of invasive procedures.

2. Old age: more likely to be exposed to situations that risk of invasive candidiasis, including Rx with broad-spectrum antibiotics , poor self-care/oral hygiene, denture & xerostomia.

3. Warm climate.4. Occlusion e.g. plastic pants (babies),

nylon pantyhose (women), dental plates. 5. Immunodeficiency e.g. low levels of

immunoglobulins, infection with HIV.

6. Broad spectrum antibiotic treatmentremoval of bacteria from the skin, vagina & GIT environmental and nutritional competition that favors the growth of candidal organisms.

7. Contraceptive pill or injection, or pregnancy.

8. Chemotherapy or immunosuppressivemedications such as systemic steroids.

9. Diabetes mellitus, Cushing's syndromeand other endocrine conditions.

10.Iron deficiency.11.General debility e.g. cancer, malnutrition.12.Underlying skin disease e.g. LP,

hyperhidrosis, psoriasis.

I. Oral candidiasis

II. Vulvovaginal candidiasis

III. Candidal Balanitis

IV. Candidal Intertrigo

V. Napkin dermatitis (nappy or diaper rash)

VI. Chronic paronychia & Onychomycosis

VII. Chronic mucocutaneous candidiasis (CMC)

ORAL INFECTION OFTEN PRESENTS AS 1. Pseudomembranous form/Oral thrush

2. Atrophic form )Acute & Chronic)

3. Chronic hyperplastic form

4. Median rhomboid glossitis.

5. Denture stomatitis.

6. Angular cheilitis (perlèche).

• Seen in children and in adults of all ages.• Acquired from the infected maternal mucosa during

passage of the infant through the birth canal.• Lesions become visible as pearly patches or

plaques or flecks (like curdled milk or cottage cheese) onthe mucosal surface.

• Buccal epithelium, gums, and the palate are involved with extension to tongue, pharynx or esophagus in severe cases.

• Lesions may progress to symptomatic erosion & ulcerationburning sensation.• The pseudomembranous lesions are easily removed. If scraped away, an

erythematous base is exposed, bleeding or even shallow ulceration.

• 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 causeof immunosuppression, such as malignancy or AIDS.

• With denture stomatitis, the areas of erythema may be painful and may affect up to 65% of patients who wear dentures.

• Occurs as plaques that are present on the buccal, palatal, or oropharyngeal mucosa overlying areas of mucosal erythema.

DIFFERENTIAL DIAGNOSIS

1. lichen planus

2. Leukoplakia

3. Chemical burns: The superficial white material burn of oral mucosa appears thin and delicate as compared to pseudomembranous candidiasis.

4. Gangrenous stomatitis: pseudomembrane is dirty in color & not raised above the surface

• Red patch of atrophic or Erythematous rawand painful mucosa with minimal evidence of the white pseudo-membranous lesions observed in thrush.

• Depapillation of tongue occurs.

• Patients after therapy with broad-spectrumantibiotics or with chronic iron deficiencyanemia may develop atrophic candidiasis.

• Includes a variety of clinically recognized conditions in which yeast invasion of the deeper layers of the mucosa and skin occurs, causing a proliferative response of hosttissue.

• CANDIDAL LEUKOPLAKIA is considered a chronic form of oral candidiasis in which firmwhite leathery plaques are detected.

• It usually affects smokers and is pre-malignant.

• Red patches (ERYTHROPLAKIA) as well as white patches may indicate malignantchange.

• Erythematous patches of atrophicpapillae located in the centralarea of the dorsum of the tongue.

• Presents as chronic mucosal erythema typically beneath the site of a denture.

• Candida spp. act as an endogenous infectingagent on tissue predisposed by chronictrauma to microbial invasion. Yeast may reproduce, undisturbed, in the space between the denture and mucosa.

• Palatal petechiae, diffuse erythema or tissue granulation or nodularity (papillary hyperplasia).

• Soreness and cracks at the lateral angles of the mouth.

• Overlap of the skin at the angles of the mouth, which is common in edentulousand elderly patients, contributing factors; 1. Use of orthodontic appliances

2. Drooling

3. Atopic dermatitis

4. (Occasionally) iron or vitamin deficiencies (e.g. B2).

• It is a common condition in women.• 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 (a substrate on which Candida albicansthrives).

• Candidal colonization of vaginal mucosa is estrogen dependent and subsequently decreases sharply after menopause.

• Presents with itching, soreness, and a thick creamy whitedischarge.

• Curdy white flecks within the discharge.• Erythema of vaginal mucosa and vulval skin sometimes

spreading widely in the groin to include pubic areas, inguinal areas and thighs.

• Erythema may spread to include the perineum & groinwith satellite pustules.

• Alternatively, the vaginal mucosa may appear red and glazed.

• Vulvovaginal candidiasis may recur just before each menstrual cycle (CYCLIC VULVOVAGINITIS).

• Symptoms may sometimes be aggravated by sexualintercourse.

• Signs and symptoms of this candidal infection vary but may include itching, erythema, oozing, tiny papules, pustules, vesicles, or persistent ulcerations on the glans penis.

• Exacerbations following intercourse are common.

1. Contact Dermatitis e.g. to rubber condoms, fragrances or medicament

2. Flexural psoriasis3. Fixed drug eruption4. Lichen planus5. Lichen sclerosus6. Penile intraepithelial neoplasia7. Syphilis8. Scabies

• Most cases occur in skin folds where occlusion (by clothing or shoes) produces abnormally moist conditions.

• The most common sites of involvement are submammary, inguinal creases, interglutealfold and the scrotum.

• Other sites include the perineum, and anus, in which Candida organisms normally may be carried.

• Patches with marked erythema, peeling, cracking, and maceration, erosion with soreness and pruriticsymptoms.

• Lesions typically have an irregularmargin with surrounding satellitepapules 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.

• Typically affect web space between the third and fourth fingers.

• Especially in individuals whose hands are frequently exposed to water.

• 85-90% of infants harbor C. albicansin the intestine and feces and in most patients, CDD is the result of progressive colonization from oraland gastrointestinal candidiasis.

FACTORS PREDISPOSING TO INFECTION:

1. Infected stools

2. Macerated moist skin

3. Local irritation of the skin by friction

4. Ammonia from bacterial breakdown of urea

5. Intestinal enzymes

6. Detergents and disinfectants

• Maceration of the anal mucosa and the perianal skin often is the first clinical manifestation.

• Usually it starts in the perianal area, spreading to involve the perineumand, in severe cases, the upper thighs, lower abdomen, and lower back.

• The typical eruption begins with scalypapules that merge to form well-defined, weeping, eroded lesions with a scallopedborder.

• A collar of overhanging scales and an erythematous base may be demonstrated.

• Satellite flaccid papules or pustules around the primary intertriginous plaque are also characteristic.

• Candida species (not always C. albicans) can be isolated from most patients.

• Gram negative bacteria also may act as co-pathogens.

• Disease is more common in people who frequently submerge their hands in

water and in diabetics.

• The nail fold becomes erythematous, swollen, and tender, with an occasional discharge.

• It may start in one nail fold but often spreads to several others.

• Loss of the cuticle occurs, along with nail dystrophy and onycholysis with discoloration around the lateral nail fold.

• A white, yellow or greenish color with hyponychial fluid accumulation may occur that results entirely from Candida, and not Pseudomonasinfection.

• Usually leads to Candida infection of the nail plate (onychomycosis). The nail may show onycholysis and is tenderness on pressure.

• CMC is a rare condition characterized by progressive, persistent and recurrent infections of the skin, nails and mucous membranes with Candida albicans occurring in childhood (60-80% of cases).

• Rarely, it develops in adult life. This is often as a result of a thymoma and is associated with internal diseases such as myasthenia gravis, myositis, aplastic anemia, neutropenia and hypogammaglobulinemia.

• It may be associated with: 1. Genetic predisposition with AD inheritance or AR inheritance.

2. Endocrinopathies e.g. hypoparathyroidism, hypothyroidism, hypoadrenalism, diabetes mellitus.

3. Immune defects i.e. malfunctioning T-lymphocytes (usually selective defect in cell-mediated immunity), low levels of immunoglobulin. Absent delayed-type hypersensitivity (DTH) in response to Candida.

PRESENTATION:• Infants often present with recalcitrant thrush,

candidal diaper dermatitis, or both.• More extensive scaling of skin lesions • Nails shows paronychia and candidal

onychomycosis markedly thickened, fragmented, and discolored, with significant edema and erythema of the surrounding periungual tissue, simulating clubbing.

• Oral involvement may extend to the esophagus, but further extension is extremely uncommon.

• Widespread candidiasis of the skin, especially scalp, periorificial, trunk, hands and feet.

• Skin lesions more frequently are acral and characterized by erythematous, crusted, hyperkeratotic, serpiginous granulomatous plaques.

• The scalp may be involved with similar hyperkeratotic plaques, which can result in scarring alopecia.

• Systemic candidiasis is rare, but cutaneousdermatophyte infections are common.

1. Familial “pure” CMC2. Chronic localized candidiasis

(“candidal granuloma”)3. Autoimmune

Polyendocrinopathy–Candidiasis–Ectodermal Dystrophy Syndrome, (APECED).

4. Late-onset CMC5. Familial chronic nail candidiasis6. CMC associated with keratitis

7. CMC associated with other immunodeficiency disorders

i. Severe combined immunodeficiency ii. DiGeorge syndrome iii. Hyper-IgE syndrome

8. CMC associated with predominantly non-immunologic conditions

i. KID syndromeii. Multiple carboxylase deficiencyiii. Acrodermatitis enteropathicaiv. Ectodermal dysplasia–ectrodactyly–

clefting syndrome

I. DIRECT MICROSCOPICAL EXAMINATION: scrapping or swab e.g. KOH Budding yeast &/or pseudohyphae &/or septate hyphae.

II. FUNGAL CULTURE: On Saboraud agar, a 48-72 hours at temperature of 370

whitecolonies.

III. HISTOPATHOLOGICAL EXAMINATION OF SKIN OR MUCOSAL BIOPSY.

SPECIAL STAINS FOR CANDIDIASIS:1. Gomori methenamine silver stain

(GMS). The stain highlights the pseudohyphal or hyphal forms penetrating into the keratinized epithelium. In addition, there are yeast-like forms in the superficial stratum corneum.

2. PAS stain can also be used to highlight the organisms.

• The characteristic feature is the presence of neutrophils in the stratumcorneum and upper layers of the epidermis. The neutrophils may form small collections (spongiformpostulation) which resembles impetigoor psoriasis.

• In the epidermis irregular acanthosis, mild spongiosis and inflammatorychanges.

• In oral lesions: ulceration of the surface covered with a fibrinoid exudate rich in yeast and pseudohyphae.

A. GENERAL MEASURES: “6”1. Identifying and removing predisposing factors is very important in the management

of mucocutaneous candidiasis e.g. control DM, correct iron deficiency, wearingcotton underwear and loose fitting clothing.

2. Personal hygiene & use of a non-soap cleanser or aqueous cream for washing then completely dry the genital areas, intertriginous areas, hands.

3. Regular use of antiseptics to clean dentures.4. Avoid wet work, or use totally waterproof gloves. 5. Apply mild steroid cream intermittently, to reduce itching and treat secondary

dermatitis affecting the vulva, glans. 6. The consumption of yogurt two to three times per week and improved oral hygiene

may also help oral candidiasis, especially if underlying predisposing factors cannot be eliminated but have not been shown to help in candidal vulvovaginitis.

B. TOPICAL TREATMENT: “6”1. Azole antifungals—Clotrimazole, miconazole or econazole cream or gel (twice

daily)/oral troche (one oral troche dissolved in mouth five times daily)/pessaries or vaginal tablets.

2. 1% gentian violet—can be used but it is not ideal because of the superficial necrosis of mucosa and it may produce unsightly staining.

3. Nystatin preparations– rinse or drops (7-10 days rinse, 3-4 times daily).4. Amphotericin-B—5-10ml of oral solution is used as a rinse and then expectorated 3-4

times daily.5. Idoquinol—it has both antifungal and antibacterial properties. When this is combined

with corticosteroid is very helpful in management of angular cheilitis.6. Boric acid 600mg as a suppository at night may help to acidify the vagina and reduce

the presence of yeasts.

C. SYSTEMIC THERAPY

• If Candida albicans infection is severe, recurrent or onychomycosis, includes the use of any one of these “3” oral antifungals:

1. Fluconazole: 150 mg single dose or once/week2. Itraconazole: 100 to 200 mg/d for 2 Weeks or pulsed-dose regimen3. Ketoconazole: once-daily dose of 200 mg

• CMC often needs longer-term and higher doses than is normally necessary for candida infections (fluconazole 100-400 mg/d or itraconazole at a dose of 200-600 mg/d until the patient improves) but standard topical medications and attempts at immune enhancement are usually ineffective.

• Fluconazole and amphotericin B may be used intravenously for the treatment of the resistant lesions of CMC and systemic candidiasis.

• Patients for whom predisposing factors such as xerostomia and immunodeficiency cannot be eliminated may need either continuous or repeated treatment to prevent recurrences.

• To prevent recurrences oral antifungals (itraconazole or fluconazole) may be taken regularly and intermittently (e.g. once a month).

• CMC initial therapy followed by maintenance therapy with the same azole for life.

• Ihab Younis, M.D. Fungal skin infections (Presentation)

• http://dermnetnz.org

• Google images

• Bolognia 3rd ed.

• http://www.mayomedicallaboratories.com

• Oral Candidiasis by Hemam Shankar Singh)Presentation(

References