Candida & Superficial Mycoses

Superficial mycoses are fungal infections limited to the keratinised layers of skin, hair and nails (and contiguous mucosae), with little or no host inflammatory response. This topic clubs the yeast Candida (commensal turned opportunist), the lipophilic yeast Malassezia, the dermatophytes (Trichophyton, Microsporum, Epidermophyton) and the hair-shaft fungi causing piedra. Lab identification tricks here are an examiner's favourite, so anchor every organism to its signature test.

Classification of fungal infections by depth

The single most testable framework is the depth-based classification. Memorise where each player sits.

Category	Tissue involved	Example organisms	Inflammation
Superficial	Outermost keratin / hair shaft only	Malassezia (pityriasis versicolor), Hortaea werneckii (tinea nigra), Piedra	Nil / minimal
Cutaneous	Keratinised epidermis, hair, nail	Dermatophytes (Trichophyton, Microsporum, Epidermophyton), Candida (mucocutaneous)	Variable
Subcutaneous	Dermis, subcutaneous tissue	Sporothrix, mycetoma agents, chromoblastomycosis	Granulomatous
Systemic / deep	Internal organs, blood	Histoplasma, Blastomyces, Coccidioides, Cryptococcus, invasive Candida	Marked

High-yield: Candida spans the spectrum — it causes superficial thrush in the immunocompetent and life-threatening candidaemia in neutropenic/ICU patients. It is the most common cause of fungal infection overall.

Candida

Microbiology & classification

Candida are oval, budding, Gram-positive yeasts (3–6 µm) that are part of normal flora of the GI tract, mouth, vagina and skin. C. albicans is the commonest species, followed by C. glabrata, C. tropicalis, C. parapsilosis, C. krusei and the emerging multidrug-resistant C. auris.

A defining morphological feature: Candida is dimorphic in the sense that it forms yeasts, pseudohyphae and true hyphae. In tissue, the presence of pseudohyphae/hyphae signals active invasion, whereas blastospores alone may be commensal.

Pathogenesis & risk factors

Candida is an opportunist — disease follows breach of the "host barrier" rather than acquisition of a new organism. The classic predisposing situations:

Extremes of age + Antibiotics (broad-spectrum) + Diabetes + Steroids/immunosuppression + Indwelling catheters/TPN + Neutropenia → candidiasis.

Virulence factors worth remembering: adhesins, germ-tube/hyphal switching (phenotypic switching), secreted aspartyl proteases (SAPs), phospholipases and biofilm formation on catheters and prosthetic material.

Clinical syndromes

• Oral thrush (pseudomembranous candidiasis): white curd-like plaques that scrape off leaving a raw bleeding base. Seen in neonates, denture wearers, inhaled-steroid users and HIV. Oesophageal candidiasis is an AIDS-defining illness (CD4 < 200, retrosternal odynophagia).
• Vulvovaginitis: thick "cottage-cheese" discharge, intense pruritus, normal pH (< 4.5). Predisposed by pregnancy, diabetes, OCPs, antibiotics.
• Cutaneous/intertrigo: moist macerated flexures (groin, submammary, web spaces — "erosio interdigitalis blastomycetica") with satellite pustules (a key clue).
• Candidal paronychia/onychomycosis: chronic in wet-work occupations.
• Chronic mucocutaneous candidiasis (CMC): persistent skin/nail/mucosal candidiasis from T-cell defects, AIRE mutation (APECED/APS-1) or STAT1 gain-of-function.
• Invasive candidiasis / candidaemia: the leading cause of fungal bloodstream infection in ICUs. Complications: endophthalmitis (mandatory fundoscopy), endocarditis (esp. C. parapsilosis with prosthetic valves and TPN), hepatosplenic candidiasis, renal abscess.

High-yield: Candida is the commonest cause of nosocomial fungal UTI and a top cause of catheter-related bloodstream infection. Always remove/replace the line.

Diagnosis — the lab tricks

1. Germ tube test (Reynolds–Braude phenomenon): incubate yeast in serum at 37 °C for 2–3 hours → C. albicans (and C. dubliniensis) produce a germ tube — a filamentous outgrowth with no constriction at its base with the mother cell. This is the rapid bedside speciation test.
2. Chlamydospore production on cornmeal–Tween 80 agar → terminal thick-walled chlamydospores are characteristic of C. albicans.
3. CHROMagar: C. albicans = green, C. tropicalis = blue, C. krusei = pink/rough.
4. Sugar assimilation/fermentation for definitive speciation.
5. Tissue/KOH: budding yeasts with pseudohyphae. Culture on Sabouraud dextrose agar (SDA) → creamy, pasty colonies; "feet" of submerged pseudohyphae.
6. Serum (1→3)-β-D-glucan is a useful adjunct for invasive disease (also positive in Aspergillus, Pneumocystis).

High-yield: Germ tube positive + no basal constriction = C. albicans. A constriction at the base ("sausage with a pinch") indicates a pseudohypha, not a true germ tube — a classic distractor.

Speciation flow: Yeast on Gram stain → Germ tube test → positive ⇒ C. albicans / C. dubliniensis; negative ⇒ CHROMagar / assimilation. C. dubliniensis is distinguished from C. albicans by no growth at 45 °C and dark-green CHROMagar colonies.

Treatment & drug of choice

Setting	Drug of choice
Oral/oesophageal thrush	Oral fluconazole; topical nystatin/clotrimazole for mild oral disease
Vulvovaginal candidiasis	Single-dose oral fluconazole 150 mg or topical azole
Cutaneous candidiasis	Topical azole/nystatin + keep area dry
Candidaemia / invasive (stable or unstable)	Echinocandin (caspofungin/micafungin/anidulafungin) first-line
C. krusei	Echinocandin (intrinsically fluconazole-resistant)
C. glabrata	Echinocandin (dose-dependent azole resistance)
C. auris	Echinocandin; often multidrug-resistant — strict infection control

High-yield: First-line for candidaemia today is an echinocandin, not amphotericin B or fluconazole. Always remove the central line and do a dilated fundus exam for endophthalmitis.

Malassezia furfur

A lipophilic, lipid-dependent yeast of normal skin flora. Requires exogenous fatty acids — hence culture needs olive oil overlay on SDA.

• Pityriasis (tinea) versicolor: hypo- or hyperpigmented, finely scaly macules on the upper trunk; fine "furfuraceous" scaling on stretching (Besnier's / evoked-scale sign). Hypopigmentation results from azelaic acid inhibiting tyrosinase in melanocytes.
• Malassezia (Pityrosporum) folliculitis, seborrhoeic dermatitis/dandruff, and catheter-associated fungaemia in neonates/adults on lipid TPN (the lipid emulsion feeds the yeast).

Diagnosis

• KOH mount: the iconic "spaghetti and meatballs" appearance — short stubby hyphae (spaghetti) + clusters of round yeasts (meatballs).
• Wood's lamp: pale yellow-green / golden fluorescence.

High-yield: KOH spaghetti-and-meatballs = Malassezia furfur. Culture is rarely done; if needed, overlay SDA with olive oil.

Treatment

Topical selenium sulphide, ketoconazole shampoo, or topical azoles; oral itraconazole/fluconazole for extensive/recurrent disease. Counsel that pigment normalises slowly over weeks–months even after cure — recurrence is common.

Dermatophytes (Tinea / Ringworm)

Three genera that digest keratin via keratinases: Trichophyton, Microsporum, Epidermophyton. They are classified ecologically as anthropophilic (human, mild chronic infection — least inflammation), zoophilic (animal, intense inflammation) and geophilic (soil). Highly inflammatory lesions usually = zoophilic source.

Who attacks what

Genus	Infects skin	Infects hair	Infects nail
Trichophyton	Yes	Yes	Yes
Microsporum	Yes	Yes	No
Epidermophyton	Yes	No	Yes

Mnemonic: Microsporum spares Nails; Epidermophyton spares Hair; Trichophyton spares nothing (all three).

Macroconidia identity (very high-yield)

Genus	Macroconidia	Microconidia
Microsporum	Spindle-shaped, thick rough (echinulate) walls, multi-septate	Few
Trichophyton	Pencil/cigar-shaped, thin smooth walls, scanty	Numerous (en grappe / en thyrse)
Epidermophyton	Club / beaver-tail-shaped, smooth, in clusters, no microconidia	Absent

Clinical "tinea" syndromes

• Tinea capitis (scalp): children; T. tonsurans (commonest in many regions, endothrix → black-dot), M. canis/audouinii (ectothrix). Kerion = boggy inflammatory mass (zoophilic). Favus = T. schoenleinii, scutula with mousy odour.
• Tinea corporis (body): annular plaque, central clearing, active scaly advancing edge.
• Tinea cruris (groin, "jock itch"), tinea pedis (athlete's foot, T. rubrum), tinea unguium/onychomycosis (T. rubrum), tinea barbae, tinea manuum ("two-feet-one-hand" syndrome).
• Id reaction (dermatophytid): sterile vesicular eruption (often hands) due to hypersensitivity to a distant focus.

Diagnosis

• KOH (10–20%) mount of skin scrapings/hair/nail → branching septate hyphae with arthrospores. KOH is the investigation of choice for screening.
• Culture on SDA (with cycloheximide + chloramphenicol) for speciation — gold standard but slow (1–4 weeks).
• Wood's lamp: Microsporum (ectothrix) fluoresces bright green; most Trichophyton (endothrix) do not fluoresce. (Favus → dull blue-green.)
• Ectothrix vs endothrix: in endothrix, spores are inside the shaft (hair breaks at scalp → black dots) and there is no fluorescence; in ectothrix, spores coat the outside and fluoresce.

High-yield: Wood's lamp positive green fluorescence in tinea capitis ⇒ think Microsporum (ectothrix). T. tonsurans (endothrix, black-dot) does not fluoresce.

Treatment

• Localised skin disease: topical terbinafine/azoles (clotrimazole, ketoconazole) for 2–4 weeks.
• Tinea capitis & onychomycosis (and extensive/resistant disease): require systemic therapy — topical agents cannot reach hair/nail keratin.
• Drug of choice for tinea capitis: oral griseofulvin (esp. Microsporum), or terbinafine (preferred for Trichophyton tonsurans).
• Onychomycosis DOC: oral terbinafine (fungicidal, best nail penetration; pulse itraconazole is an alternative).

High-yield: Griseofulvin acts by binding tubulin and disrupting the microtubule mitotic spindle; absorption improves with a fatty meal. Terbinafine inhibits squalene epoxidase (squalene accumulation is fungicidal).

Piedra (hair-shaft nodular infections)

Feature	Black piedra	White piedra
Organism	Piedraia hortae (a dematiaceous mould)	Trichosporon spp. (yeast; e.g. T. beigelii/ovoides/inkin)
Nodule	Hard, gritty, firmly adherent, dark	Soft, pale, loosely attached, white-tan
Site	Scalp hair	Beard, axilla, groin, scalp
Note	Asci with ascospores in nodule	Trichosporon can cause disseminated infection in neutropenics; cross-reacts with cryptococcal antigen latex test

High-yield: Trichosporon (white piedra) is urease-positive and can give a false-positive cryptococcal antigen test; it causes fatal disseminated trichosporonosis in neutropenic patients.

Tinea nigra (bonus superficial mycosis)

Caused by Hortaea (Exophiala) werneckii — a dematiaceous fungus producing a painless brown-black macule on the palm/sole. KOH shows brown branching septate hyphae. Important because it mimics acral melanoma; treat with topical keratolytics/azoles.

Key differentials

• Pityriasis versicolor vs vitiligo (no scale, complete depigmentation, bright white Wood's) vs pityriasis alba (ill-defined, atopic children) vs tinea corporis (annular with active edge).
• Oral thrush vs oral hairy leukoplakia (EBV, lateral tongue, does not scrape off) vs lichen planus (Wickham striae).
• Candidal intertrigo (satellite pustules, beefy red) vs tinea cruris (advancing scaly margin, central clearing, spares scrotum) vs erythrasma (Corynebacterium minutissimum, coral-red Wood's fluorescence).
• Onychomycosis vs psoriatic nail (pitting, oil-drop sign).

Recently asked / exam angle

• Image/specimen-based: "Spaghetti and meatballs on KOH" → Malassezia furfur; "germ tube positive yeast" → C. albicans; "spindle-shaped echinulate macroconidia" → Microsporum.
• DOC reversals: First-line for candidaemia is now an echinocandin (a frequent update question, replacing the older amphotericin/fluconazole answers). C. krusei — pick the non-fluconazole option.
• Wood's lamp colour matching: Microsporum green, erythrasma coral-red, Malassezia golden-yellow, Pseudomonas/tinea favus — classic single-best-answer grid.
• Mechanism MCQs: griseofulvin → microtubule/spindle; terbinafine → squalene epoxidase; azoles → 14-α-demethylase (lanosterol → ergosterol); echinocandins → β-1,3-glucan synthase.
• Special media: Malassezia needs olive oil overlay; C. albicans chlamydospores on cornmeal-Tween 80 agar; dermatophytes on SDA + cycloheximide.
• HIV/immunology link: oesophageal candidiasis = AIDS-defining; CMC with hypoparathyroidism + Addison's = APECED (AIRE gene).

Rapid revision

1. C. albicans — germ tube positive with no basal constriction; chlamydospores on cornmeal-Tween 80; green on CHROMagar.
2. Candidaemia DOC = echinocandin; always remove the line and examine the fundus for endophthalmitis.
3. C. krusei = intrinsically fluconazole-resistant; C. auris = multidrug-resistant, infection-control nightmare.
4. Vulvovaginal candidiasis = thick curdy discharge, normal vaginal pH, single-dose fluconazole.
5. Malassezia furfur = spaghetti-and-meatballs KOH, golden Wood's fluorescence, needs olive oil to culture; hypopigmentation via azelaic acid.
6. Dermatophyte rule: Microsporum spares Nails; Epidermophyton spares Hair; Trichophyton spares neither.
7. Macroconidia: Microsporum = spindle rough; Trichophyton = thin pencil-shaped; Epidermophyton = club/beaver-tail in clusters.
8. KOH = screening IOC, SDA culture = gold standard for dermatophytes.
9. Microsporum (ectothrix) fluoresces green; T. tonsurans (endothrix, black-dot) does not; black-dot tinea capitis is endothrix.
10. Griseofulvin for Microsporum tinea capitis; terbinafine DOC for onychomycosis and T. tonsurans.
11. Black piedra = Piedraia hortae (hard nodule); white piedra = Trichosporon (soft nodule, urease+, false-positive cryptococcal antigen).
12. Tinea nigra = Hortaea werneckii on palm/sole — mimics acral melanoma.