Mycoses

Question 1

Fungal Infections (Mycoses)

Classification

Answer 1

Typically classified according to tissue level primarily infected:

• Superficial (skin or mucosa)
  
  • Mycoses caused by fungi that colonize the outer keratinized, non-living, layers of skin and hair
• Cutaneous
  
  • Mycoses are common
  • Caused by dermatophytes
  • Can invade the outermost layer of the epidermis, including the hair and nails
• Subcutaneous
  
  • Typically initiated by traumatic inoculation of the fungus through damage to the skin
  • Can involve dermis, subQ, muscle, fascia, and in some instances lymphatic tissue
• Mucosal (Opportunistic)
  
  • Most typically vaginal and oropharyngeal
  • Caused by candida species
    
    • Opportunistic yeast that normally inhabits these sites
• Systemic
  
  • “True pathogens”
    
    • Infect healthy hosts
  • “Opportunists”
    
    • Disease almost exclusively in immunocompromised

Question 2

Superficial Mycoses

Overview

Answer 2

Infection of the stratum corneum

• Etiologies:
  
  • Malassezia furfur and globosa
    
    • Lipophilic yeast
• Disease:
  
  • Pityriasis versicolor (“Tinea versicolor”)
  • Fungemia with lipid infusions

Question 3

Malassezia

Morphology

Answer 3

Clusters of thick-walled yeast cells mixed with hyphae

“Spaghetti and Meat Balls”

Question 4

Malassezia

Epidemiology & Transmission

Answer 4

• Worldwide distribution particularly in tropical and subtropical regions
• Most common in young adults
• Spread by transfer of infected skin and person-to-person contact

Question 5

Pityriasis Versicolor

Clinical Symptoms

Answer 5

• Hyper and hypopigmentation of upper torso and arms, that can be scaled
  
  • Skin lesions fluoresce under a Wood (UV) lamp
• Can cause dandruff and seborrheic dermatitis
• Generates little or no host immune response

Question 6

Pityriasis Versicolor

Diagnosis

Answer 6

• Requires culture in the presence of lipids
• Visualization of fungus, “spaghetti and meat balls”, from epidermal sample treated with KOH
• Skin lesions fluoresce under a wood (UV) lamp

Question 7

Pityriasis Versicolor

Treatment

Answer 7

Topical azoles

Anti-fungal shampoos (selenium sulfide)

Question 8

Cutaneous Mycoses

Overview

Answer 8

“Dermatophytosis”

• Caused by Dermatophytes
• Comprised of filamentous fungal species from three genera:
  
  • Trichophyton
  • Epidermophyton
  • Microsporum

Question 9

Dermatophytes

Morphology

Answer 9

• Hyaline septate hyphae, chains or arthroconidia, or dissociated chains of arthroconidia
• Classified by presence and characteristics of macroconidia and microconidia in culture:
  
  • Epidermophyton ⇒ do not produce microconidia
  • Trichophyton ⇒ produce many microconidia
  • Microsporum ⇒ identified by its macroconidia

Question 10

Dermatophytes

Ecology

Answer 10

• Worldwide distribution
• Individual species w/ distinct geographical regions & ecological niches
• Are not members of the normal flora
• Ability to survive on wet surfaces, likely contributing to transmission

Question 11

Dermatophytes

Epidemiology & Transmission

Answer 11

• Transmission via transfer of arthroconidia or hyphae
  
  • Need exposure & break in the skin
• Both sexes and all ages are susceptible to dermatophytosis
• Some are more common in specific genders or age groups
  
  • Tinea pedis has a preference for infecting males
  • Tinea capitis is more common in prepubescent children
• Site of infection can be influenced by age of host
• Overall incidence higher in males than in females
  
  • Ratios of 3:1 for tinea capitis and 6:1 for tinea pedis
• Worldwide, T. rubrum and T. mentagrophytes account for 80-90% of infections

Question 12

Cutaneous Mycoses

Pathogenesis

Answer 12

• Dermatophytes invade the skin, hair or nails
• Patterns of invation can be either:
  
  • Ectotrix ⇒ remains confined to hair surface
  • Endotrix ⇒ invades the hair shaft and internalizes into hair cell
  • Favic ⇒ saucer-shaped crusted lesions or scutula
• Fungi are keratinophilic & keratinolytic
  
  • Can breakdown keratin to gain entry to the uppermost layer of skin
  • Secrete keratinase
• Typically invade only the upper outermost layer of the epidermis, the stratum corneum
• Penetration below the granular layer of the epidermis rare

Question 13

Cutaneous Mycoses

Clinical Symptoms

Answer 13

• Dermatophyte infections called “tineas”
• Subdivided according to site infected
• Clinical signs and symptoms vary according to the etiologic agents, host reaction, and site of infection
• Dermatophytes spread though stratum corneum, outward from point of infection, giving a characteristic ring shape ⇒ “ring worm”
• Viable fungi are at the perimeter of the ring
• Fungal invasion of the nails occurs through the lateral or superficial nail plates then spreads throughout the nail
• When hair shafts are invaded, organisms can be seen either within the shaft or surrounding it
• Rash is often erythematous

Question 14

Cutaneous Mycoses

Sites of Infection

Answer 14

Question 15

Tinea Capitis

Answer 15

Hair & Scalp

• Presents with well-demarcated scaly patches
• Hair shafts have broken off right above the skin
• Most commonly T. tonsurans (endothrix)
• Fluoresce green under wood’s (UV) lamp

Question 16

Tinea Pedis

Answer 16

Feet

Causes fissures between toes and erythematous, scaly, pruritic rash along lateral and plantar surfaces of feet

Question 17

Tinea Corporis

Answer 17

Ringworm of the body

• Well-demarcated, pruritic, scaly lesions
• Undergo central clearing as the lesion expands
• Often 1 or more small lesions are present
• More extensive involvement less likely

Question 18

Tinea Cruris

Answer 18

Ringworm of the groin; “jock itch”

Pruritic, erythematous rash with scaly border in the groin area

Question 19

Tinea Unguium

Answer 19

Ringworm of the nail, a.k.a. Onychomycosis

• Caused by a variety of dermatophytes
• Estimated to affect ~3% of the population in most temperate countries
• Mostly seen in adults
• More commonly affects toenails than fingernails
• Infection is usually chronic
• Nails become thickened, discolored, raised, friable, and deformed
• T. rubrum is most common etiologic agent
  
  • Can also be caused by candida

Question 20

Tinea Barbae

Answer 20

Ringworm of the beard

Question 21

Cutaneous Mycoses

Laboratory Diagnosis

Answer 21

• KOH treatment of skin/sample
• Microscopic observation of hyaline, septate, branching hyphae confirms dx of dermatophyte infection
• Culture is required to identify specific species
• Macroconidia and microconidia can be observed after culture in mycosel or mycobiotic agar selective for dermatophytes
  
  • Contains cycloheximide and chloramphenicol

Question 22

Cutaneous Mycoses

Treatment

Answer 22

For most localized non-hair and non-nail infections:

• Topical treatment with specific antifungal (azoles, allylamines) is usually sufficient
• Nail lacquers for onychomycosis can be used in mild cases
• Otherwise oral terbinafine
  
  • Especially with any severe infection or in immunocompromised patients
• Successful therapy of nail infection may require many months
• Discontinuation of therapy before then may result in relapses

Question 23

Subcutaneous Mycoses

Overview

Answer 23

• Caused by fungi that normally reside in soil
• Typically initiated by traumatic inoculation of the fungus through damage to the skin
• Infections and can involve dermis, subcutaneous, muscle, fascia, and in some instances lymphatic tissue
  
  • Can rarely become systemic
• Infection is chronic and hard to treat
• Sporotrichosis caused by Sporothrix schenckii is the most common infection

Question 24

Sporothrix schenckii

Morphology

Answer 24

• Thermally dimorphic
  
  • Ambient temperatures (25°C) grows as a mold w/ septate hyphae & conidia that contain melanin
  • 37°C grows as small budding yeast
• Mycelial-form cultures grow rapidly
• Wrinkled membranous surface that gradually becomes tan, brown, or black
• Microscopically:
  
  • Mold form consists of narrow, hyaline, septate hyphae
  • Produce abundant oval conidia

Question 25

Sporotrichosis Epidemiology

Answer 25

**"Rose Pickers Disease"** * Warmer climates including North and South America * Outbreaks of infection related to **forest work, mining, and gardening** have occurred * Classic infection is associated with traumatic inoculation of soil or vegetable or organic matter contaminated with the fungus

Question 26

Sporotrichosis Clinical Symptoms

Answer 26

Rose Pickers Disease * Classically appears after **local trauma to an extremity** * **Nodule** appears at site of initial infection * **Spreads through lymphatic system** creating additional nodules * **Secondary lymphatic nodules** appear ~ 2 weeks s/p appearance of the primary lesion ⇒ **linear chain of painless subcutaneous nodules** * Extend proximally along the course of lymphatic drainage of the primary lesion * Lesions may ulcerate * Very occasionally disseminates

Question 27

Sporotrichosis Laboratory Diagnosis

Answer 27

Definitive diagnosis depends on culture of the infected pus or tissue ## Footnote **At 25°C ⇒ hyphal form grows** **At 35°C ⇒ yeast form grows**

Question 28

Sporotrichosis Treatment

Answer 28

Low-cost treatment is oral saturated potassium iodide daily for 3-4 weeks Itraconazole better

Question 29

Opportunistic Mycoses

Answer 29

* **Primary location of infection includes oral, vaginal, urinary tract, and intestinal** * Most commonly caused by **Candida albicans** * Typically part of normal flora

Question 30

Candidiasis Overview

Answer 30

* Most important group of **opportunistic fungal pathogens** * Candida albicans can cause two classes of disease * Mucosal infections * Systemic infections * **90-100 % of mucosal infections are caused by C. Albicans** * Remainder by C. glabrata, C. parapsilosis, C. tropicalis, C. krusei

Question 31

Candida Morphology

Answer 31

* **C. albicans is thermally dimorphic** * **25°C ⇒ budding yeast** * **37°C ⇒ hyphae (“germ tube”)** * All candida species exist as **oval yeast-like** forms that produce **buds or blastoconidia** * Species of candida other than C. glabrata also produce **pseudohyphae and true hyphae**

Question 32

Candida Epidemiology & Transmission

Answer 32

* **Normal flora of oral cavity, genitalia, GI tract, or skin of most ppl** * Causes 80% of nosocomial fungal infections / 30% of deaths from nosocomial infections * Predominant source of infection is the patient ⇒ **endogenous infection**

Question 33

Candidiasis Risk Factors

Answer 33

Predisposing host factors cause C. albicans to change from commensal to pathogen: * _For mucosal infections:_ * **Age (very young & very old)** * **Broad- spectrum abx use** * **DM** * **HIV** * **Immunosuppression** * _For vaginal infections:_ * **Oral contraceptives**

Question 34

Candidiasis Pathogenesis

Answer 34

* **Morphogenesis** ⇒ important virulence factor * Allows rapid multiplication and dissemination in host * Yeast and hyphal forms of C. Albicans **bind epithelial and endothelial cells via specific proteins** * Proteins recognize **fibronectin** and other host proteins * Hyphae can invade host cells through the production of: * **Proteinases** * **Phospholipases** * **Lipases** * If tissue invasion continues unabated, a systemic infection can arise

Question 35

Mucocutaneous Candidiasis

Answer 35

* **Thrush** * Think, white, adherent growth on the MM of mouth and throat * **Vulvovaginal yeast infections** * Painful inflammatory condition of the female genital region * Causes ulceration and whitish discharge * **Cutaneous candidiasis** * Occurs in chronically moist areas of skin and burn pts

Question 36

Candidiasis Clinical Symptoms

Answer 36

* **Oropharyngeal (thrush) and vaginal infections** * Overgrowth of candida seen as a white “cottage cheese like” patches * **Pseudomembranous type** * Has a raw bleeding surface when scraped * **Erythematous type** * Recognized by flat red areas * **Leukoplakia** ⇒ non-removable white layer covering epithelium tissue * **Angular cheilitis** ⇒ sore corners of the mouth * Other areas of infection include the groin and breast-folds * **Onychomycosis** was discussed earlier

Question 37

Candidiasis Laboratory Diagnosis

Answer 37

* Microscopic examination of scrapings from lesions after treatment with **KOH** * **Reveals budding yeast and hyphal forms** * Visualization of characteristic **budding yeasts and pseudohyphae** is sufficient for diagnosis of candidiasis * Specimens can be **cultured on selective medium e.g. chromagar** * _Can distinguish species by colony color_ * **C. albicans ⇒ green** * **C. tropicalis ⇒ blue** * **C. krusei ⇒ pink** * **Other species ⇒ white to mauve** * **Sugar assimilation test strips** can also provide candida species identification * For suspected C. Albicans a “**germ-tube” formation test** can be performed

Question 38

Candidiasis Treatment

Answer 38

* First eliminate any predisposing factors * Skin and mucosal infections * Treated with topical creams, lotions, ointments, and suppositories containing azole antifungal agents * Recurring or chronic mucosal infections * May require oral antifungals