14.3 Superficial, Subcutaneous & Deep Mycoses

14.3 Superficial, Subcutaneous & Deep Mycoses

Overview of Medical Mycology in Dermatology

Fungal infections of the skin, hair, and nails represent one of the most common reasons for specialist dermatological consultation worldwide. Dermatotropic fungi are classified clinically and taxonomically into three major operational groups:

1. Dermatophytes: Filamentous fungi belonging to the genera Trichophyton, Microsporum, and Epidermophyton. They are keratinophilic, synthesizing specialized extracellular serine and metalloproteases (keratinases) that digest keratin, restricting their invasion to the non-living cornified layers of the skin (stratum corneum), hair shafts, and nail plates.
2. Yeasts: Unicellular fungi replicating by budding: Candida species and lipophilic dimorphic Malassezia species.
3. Molds, Dimorphic & Dematiaceous Fungi: Environmental saprophytes causing subcutaneous or systemic mycoses following transcutaneous traumatic inoculation (e.g., Sporothrix, pigmented dematiaceous fungi, and agents of mycetoma).

Dermatophytoses (Tinea)

Ecological Taxonomy: Anthropophilic, Zoophilic & Geophilic

Dermatophytes are categorized based on their natural ecological habitat and host adaptation, which directly dictates the severity of the host inflammatory response:

+--------------------------------------------------------------------------+
|                 ECOLOGICAL DICHOTOMY OF DERMATOPHYTES                    |
+--------------------------------------------------------------------------+
| ANTHROPOPHILIC (Human hosts):                                            |
| - Trichophyton rubrum (most common worldwide)                            |
| - Trichophyton interdigitale (anthropophilic strain)                     |
| - Trichophyton tonsurans (predominant tinea capitis in urban Europe/US)  |
| - Microsporum audouinii, Epidermophyton floccosum                        |
| -> Highly host-adapted; mild, indolent, non-inflammatory, CHRONIC course |
|                                                                          |
| ZOOPHILIC (Animal hosts):                                                |
| - Microsporum canis (cats, dogs, kittens)                                |
| - Trichophyton verrucosum (cattle, cattle-handlers)                      |
| - Trichophyton mentagrophytes (rodents, guinea pigs, rabbits)            |
| - Trichophyton equinum (horses)                                          |
| -> Poorly host-adapted in humans; ACUTE, intense cell-mediated reaction, |
|    exuberant suppuration, follicular pustules, KERION formation          |
|                                                                          |
| GEOPHILIC (Soil reservoir):                                              |
| - Nannizzia gypsea (formerly Microsporum gypseum)                        |
| -> Moderate-to-severe inflammatory reactions following soil exposure    |
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Anatomical Variants of Dermatophytosis

1. Tinea Capitis

• Epidemiology: Most common superficial fungal infection in prepubertal children (predominantly 3 to 10 years of age). It is rare in post-pubertal adults because pubertal sebaceous gland maturation increases secretion of sebum containing fungistatic, saturated, medium-chain fatty acids (undecylenic acid).
• Hair Invasion Patterns & Wood's Lamp Examination:
  • Endothrix Infection: Fungal arthroconidia proliferate and pack exclusively inside the hair shaft, destroying the inner hair architecture and cuticle. The weakened hair breaks flush with the scalp surface, leaving open follicular orifices stuffed with dark hyphal plugs: "black-dot tinea". Caused by anthropophilic species: Trichophyton tonsurans and Trichophyton violaceum. Wood's lamp examination is negative (no fluorescence).
  • Ectothrix Infection: Arthroconidia and hyphae form an external dense sheath around the outside of the hair shaft, destroying the cuticle. Hairs break 2 to 3 mm above the scalp level: "grey-patch tinea". Caused by zoophilic species (Microsporum canis) and anthropophilic Microsporum audouinii. Wood's Lamp Examination: Emits brilliant green-yellow fluorescence due to the fungal synthesis of pteridine.
  • Favus (Tinea Favosa): Caused by Trichophyton schoenleinii. Characterized by sulfur-yellow, cup-shaped, concave crusts centered around hair follicles termed scutula (composed of dense mycelia, epithelial debris, and sebum). Associated with a characteristic "mousy" odor and dull greenish fluorescence under Wood's lamp. Favus causes severe follicular destruction, leading to permanent cicatricial (scarring) alopecia.
• Kerion Celsi:
  • An exuberant, severe, cell-mediated delayed-type hypersensitivity reaction to a zoophilic dermatophyte (most commonly Trichophyton verrucosum from cattle or Microsporum canis from kittens).
  • Presents as an acutely tender, boggy, swollen, elevated, purulent inflammatory plaque studded with discharging pustules and draining sinus tracts, accompanied by cervical lymphadenopathy.
  • Critical Clinical Pitfall: Kerion closely mimics a bacterial scalp abscess or carbuncle. Incision and drainage is strictly contraindicated as it produces massive disfiguring tissue loss without therapeutic benefit. Systemic corticosteroids (oral prednisolone 0.5–1 mg/kg/day for 1–2 weeks) may be added to systemic antifungals in severe cases to rapidly reduce inflammation and minimize permanent scarring alopecia.
• Therapeutic Mandatory Rule: Topical antifungals alone are completely ineffective for tinea capitis because topical agents cannot penetrate down to the hair bulb. Systemic oral therapy is mandatory:
  • Trichophyton tonsurans / species: First-line is oral Terbinafine (weight-based: <20 kg: 62.5 mg/day; 20–40 kg: 125 mg/day; >40 kg: 250 mg/day for 4 to 6 weeks).
  • Microsporum canis / species: First-line is oral Griseofulvin (microsize 15–20 mg/kg/day or ultramicrosize 10–15 mg/kg/day for 8 to 12 weeks) or oral Itraconazole (3–5 mg/kg/day for 4 to 6 weeks). Terbinafine demonstrates lower mycological cure rates for Microsporum species due to lower intracellular affinity in Microsporum hair shafts.
  • Adjunctive Measures: Ketoconazole 2% or selenium sulfide 2.5% shampoo applied twice weekly to the patient and household contacts to eliminate surface spore carriage and prevent reinfection.

2. Tinea Corporis, Cruris & Pedis

• Tinea Corporis ("Ringworm"): Annular, polycyclic, sharply demarcated erythematous plaques characterized by an active, elevated, scaly advancing peripheral border with central clearing. The advancing rim contains active hyphae and microvesicles/pustules. Scrapings for microscopy must always be collected from the active advancing edge, not the cleared center.
• Tinea Cruris ("Jock Itch"): Dermatophyte infection of the groin, upper medial thighs, and perineum. Predominantly affects adolescent and adult males in warm, humid microclimates. Hallmark: An expanding scaly erythematous plaque with a raised active margin. The scrotum and penis are characteristically spared, providing an essential diagnostic contrast to candidal intertrigo and severe flexural psoriasis.
• Tinea Incognito: A bizarre, atypical, modified dermatophytosis resulting from the inappropriate, misdiagnosed application of topical corticosteroids (or topical calcineurin inhibitors). Corticosteroids suppress the host local inflammatory response: the characteristic elevated, scaly, advancing border disappears; erythema becomes faint or blotchy; and follicular pustules or telangiectasias appear. The lesion can mimic lupus erythematosus, rosacea, or eczema. Scrapings reveal teeming, extensive networks of branching septate hyphae.
• Majocchi Granuloma (Tinea Profunda): A deep, granulomatous dermatophytic folliculitis and perifolliculitis occurring when Trichophyton rubrum penetrates the disrupted follicular wall into the mid- and deep dermis, often triggered by leg-hair shaving or topical steroid misuse. Presents as tender, erythematous, violaceous follicular papules, nodules, and plaques on the lower legs of women. Requires systemic oral antifungal therapy (terbinafine 250 mg daily for 4 to 6 weeks).
• Tinea Pedis ("Athlete's Foot"):
  • Interdigital: Most common type; erythema, maceration, scaling, and painful fissuring in the lateral toe clefts (4th/5th toe webs). Serves as the primary portal of entry for lower-limb bacterial erysipelas and cellulitis.
  • Moccasin Type (Hyperkeratotic): Chronic, diffuse, silvery, fine powdery scaling on a background of dull erythema covering the sole, heel, and lateral borders of the foot ("moccasin distribution"). Driven by Trichophyton rubrum. Frequently presents as "two feet-one hand syndrome" (bilateral moccasin tinea pedis accompanied by unilateral tinea manuum involving the dominant hand).
  • Vesiculobullous Type: Acute, severely pruritic vesicles and bullae on the plantar instep and arch, caused by Trichophyton interdigitale. Frequently triggers a secondary sterile vesicular dermatophytid ("id") reaction along the lateral aspects of the fingers.

3. Onychomycosis (Tinea Unguium)

Fungal infection of the nail apparatus. Dermatophytes cause >80% to 90% of onychomycosis (T. rubrum > T. interdigitale); non-dermatophyte molds (Scopulariopsis brevicaulis, Fusarium, Aspergillus) and Candida account for the remainder.

+--------------------------------------------------------------------------+
|                    CLINICAL PATTERNS OF ONYCHOMYCOSIS                    |
+--------------------------------------------------------------------------+
| 1. Distal & Lateral Subungual (DLSO) | Most common. Hyponychium entry,  |
|                                      | subungual hyperkeratosis, onycholysis|
| 2. Superficial White (SWO)           | Direct invasion of dorsal nail   |
|                                      | plate; chalky white friable patches|
| 3. Proximal Subungual (PSO)          | Cuticle / proximal fold entry ->  |
|                                      | KEY MARKER OF SEVERE HIV / AIDS  |
| 4. Total Dystrophic (TDO)            | End-stage crumbling of full plate|
+--------------------------------------------------------------------------+

• Proximal Subungual Onychomycosis (PSO): The fungus directly penetrates under the proximal nail fold to infect the underlying nail matrix, migrating distally as a transverse white band under an intact, smooth nail plate. PSO is a classic, high-yield clinical hallmark of advanced HIV infection (CD4 <200 cells/µL) and profound iatrogenic immunosuppression.
• Treatment Guidelines for Onychomycosis:
  • Diagnostic Mandate: Because 50% of dystrophic nails are caused by non-fungal conditions (psoriasis, lichen planus, trauma, onychogryphosis), systemic antifungal therapy must never be initiated without prior mycological confirmation (KOH direct microscopy, culture, or nail clipping PAS histology).
  • First-Line Systemic Therapy: Oral Terbinafine 250 mg once daily for 6 weeks for fingernail infections and 12 weeks (3 months) for toenail infections. Terbinafine is fungicidal against dermatophytes, achieving mycological cure rates >75%. Baseline liver function tests (LFTs) are recommended.
  • Alternative Systemic Therapy: Oral Itraconazole pulse therapy: 200 mg PO twice daily (400 mg/day) for 1 week per month. Administer 2 pulses for fingernails and 3 pulses for toenails. Itraconazole is fungistatic and carries significant cytochrome P450 3A4 drug-drug interactions.
  • Topical Monotherapy: Topical nail lacquers (Amorolfine 5% applied once weekly or Ciclopirox 8% applied daily) are indicated exclusively for mild distal disease (<50% distal nail plate involvement without matrix/lunula involvement) or superficial white onychomycosis.

Diagnostic Mycological Techniques

Pityriasis (Tinea) Versicolor

Etiology & Pathogenesis

• Etiology: Caused by lipophilic, dimorphic yeasts belonging to the genus Malassezia (predominantly Malassezia globosa and Malassezia sympodialis, formerly categorized under Malassezia furfur / Pityrosporum orbiculare/ovale). Malassezia is a normal, lipid-dependent commensal organism colonizing sebum-rich cutaneous sites.
• Pathophysiological Transformation: Under the influence of heat, relative humidity, heavy perspiration, sebum secretion, or occlusive clothing, the organism shifts from its asymptomatic saprophytic round yeast phase into its pathogenic mycelial (pseudohyphal) form.
• Mechanism of Dyschromia (Hypopigmentation vs Hyperpigmentation):
  • Hypopigmentation: Malassezia oxidizes unsaturated free fatty acids in sebum to produce dicarboxylic acids, primarily azelaic acid. Azelaic acid acts as a potent competitive inhibitor of tyrosinase (the rate-limiting enzyme in melanogenesis) and exerts direct cytotoxic injury to melanocytes, halting melanin production. The yeast also secretes pityriacitrin, an indolic compound that functions as a natural ultraviolet filter.
  • Hyperpigmentation: Results from an increased thickness of the hyperkeratotic stratum corneum and an exaggerated localized inflammatory response with enlarged melanosomes.

Clinical Presentation & Diagnostic Signs

• Morphology: Multiple discrete to confluent, oval, sharply circumscribed macules and thin patches with a delicate, branny, powdery surface scale. Colors range across hypopigmented chalky-white, pink, salmon, light tan, to dark hyperpigmented brown ("versicolor").
• Distribution: Predominantly upper trunk ("v-shape" of chest and upper back), neck, and proximal upper extremities (sebum-rich distribution).
• High-Yield Diagnostic Signs:
  • Coup d'Ongle Sign (Besnier's Scratch Sign / Evoked Scale): Gently scraping the surface of an apparently smooth macule with a fingernail, curette, or tongue depressor readily cleaves and accentuates a fine, powdery, cigarette-paper-like scale.
  • Wood's Lamp Examination: Emits a faint, characteristic yellow-gold to orange-yellow fluorescence due to fluorochromes produced by Malassezia.
  • Direct KOH Microscopy: Pathognomonic "spaghetti and meatballs" (or "bananas and grapes") appearance: short, angular, bent pseudohyphae intermixed with clusters of thick-walled, round budding yeast cells (3–8 µm).

European Management Guidelines

• First-Line Topical Therapy:
  • Ketoconazole 2% shampoo: Applied to damp skin across the entire upper trunk, lathered, left in contact for 5 to 10 minutes, and rinsed off daily for 5 to 14 consecutive days.
  • Alternative topicals: Selenium sulfide 2.5% suspension or topical terbinafine 1% spray.
• Second-Line / Extensive Oral Therapy:
  • Indicated for widespread, highly recalcitrant, or frequently relapsing disease: Oral Itraconazole 200 mg once daily for 7 consecutive days, or oral Fluconazole (300 mg once weekly for 2 to 3 weeks).
  • Critical Specialist Rule: Oral Terbinafine is completely INEFFECTIVE for pityriasis versicolor. Although terbinafine is fungicidal against dermatophytes, orally administered terbinafine does not reach therapeutic concentrations in the superficial lipid mantle and stratum corneum to inhibit Malassezia.
• Maintenance Prophylaxis: Because recurrence rates approach 60% to 80% within two years, prophylactic ketoconazole 2% shampoo applied once or twice monthly prior to summer months is recommended.

Cutaneous & Mucocutaneous Candidiasis

Pathogenesis & Etiology

Caused primarily by Candida albicans (>80%), alongside non-albicans species (Candida parapsilosis, Candida tropicalis, Candida glabrata, Candida krusei). Unlike dermatophytes, Candida albicans is a normal commensal of the human gastrointestinal and female genital tract that transitions into an invasive pathogen upon host barrier breakdown, immunosuppression, or alteration of normal bacterial microbiota.

Clinical Presentations

1. Candidal Intertrigo:
   • Involves opposing, macerated skin folds: inframammary, genitocrural, axillae, intergluteal cleft, and the abdominal pannus in obese and diabetic individuals.
   • Pathognomonic Morphology: Fiery, beefy-red, glistening, moist, denuded plaques with an irregular, finely fringed macerated collarette of scale at the margin, surrounded by discrete, pinpoint satellite pustules and papules that erode into red macules beyond the primary border.
2. Oral Candidiasis:
   • Pseudomembranous (Thrush): Creamy white, curd-like plaques on buccal mucosa and tongue that can be readily scraped off with a tongue depressor, leaving a bright red, raw, bleeding mucosal base (distinguishing it from oral hairy leukoplakia, which cannot be wiped off).
   • Acute Atrophic: Fiery red, painful, depapillated "bald" tongue following broad-spectrum antibiotic therapy.
   • Angular Cheilitis (Perlèche): Erythema, maceration, and painful radial fissuring at the labial oral commissures, often co-infected with S. aureus.
3. Candidal Balanitis & Balanoposthitis: Pinpoint erythematous papules and tiny pustules on the glans penis and inner prepuce, eroding into glazed, tender erythema with curd-like subpreputial discharge; strongly associated with uncircumcised status and poorly controlled diabetes mellitus.
4. Chronic Mucocutaneous Candidiasis (CMC):
   • A group of rare primary immunodeficiency syndromes characterized by persistent, non-invasive, severely disfiguring candidal infections of the skin, nails, and oral/genital mucosa, accompanied by thick hyperkeratotic "candidal horns".
   • Underlying Molecular Genetics: Caused by genetic mutations disrupting the interleukin-17 (IL-17) signaling axis, which is essential for mucosal antifungal neutrophil recruitment:
     • Autosomal dominant STAT1 gain-of-function (GOF) mutations (impairing Th17 cell differentiation).
     • Mutations in IL17F, IL17RA, or ACT1 (TRAF3IP2).
     • APECED Syndrome (APS-1): Caused by autosomal recessive mutations in the AIRE gene (autoimmune regulator), presenting with the classic triad of chronic mucocutaneous candidiasis, hypoparathyroidism, and primary adrenocortical insufficiency (Addison disease).

Subcutaneous & Deep Mycoses

+--------------------------------------------------------------------------+
|               HALLMARKS OF SUBCUTANEOUS & DEEP MYCOSES                   |
+--------------------------------------------------------------------------+
| SPOROTRICHOSIS (Sporothrix schenckii):                                   |
| - Rose thorn inoculation -> Primary chancre -> Ascending lymphocutaneous |
| - Asteroid bodies (Splendore-Hoeppli) -> Oral ITRACONAZOLE (1st-line)     |
|                                                                          |
| MYCETOMA (Madura Foot):                                                  |
| - Triad: Painless tumefaction + Sinus tracts + FUNGAL GRAINS/GRANULES    |
| - Actinomycetoma (Bacteria, 60%): Welsh regimen (TMP-SMX + Amikacin)     |
| - Eumycetoma (Fungi, 40%, Madurella): Itraconazole + Radical Surgery     |
|                                                                          |
| CHROMOBLASTOMYCOSIS (Dematiaceous pigmented fungi):                      |
| - Traumatic inoculation -> Verrucous cauliflower-like plaques + black dots|
| - Pathognomonic: MURIFORM CELLS / MEDLAR BODIES ("Copper Pennies")       |
| - Thick-walled golden-brown cells dividing by internal cleavage          |
+--------------------------------------------------------------------------+

1. Sporotrichosis ("Rose Gardener's Disease")

• Etiology: Sporothrix schenckii complex (S. schenckii, Sporothrix brasiliensis [zoonotic transmission via domestic cat scratches/bites in Latin America]). It is a thermally dimorphic fungus existing as a branching hyphal mold with floral conidia at environmental temperatures (25°C) and transitioning into a small, elongated, budding "cigar-shaped" yeast in host tissues at 37°C.
• Transmission: Traumatic transcutaneous implantation from contaminated plant matter: rose thorns, sphagnum moss, bark, or decaying wood.
• Clinical Presentation (Lymphocutaneous Sporotrichosis):
  • Begins several weeks following inoculation as a painless, firm, erythematous subcutaneous nodule at the puncture site (most commonly the hand or finger), which ulcerates to form a sporotrichotic chancre.
  • Over subsequent weeks, secondary subcutaneous nodules erupt in a linear fashion along the draining regional lymphatic vessels proximal to the primary lesion (ascending sporotrichoid lymphocutaneous spread). These nodules indurate, fluctuant, and may ulcerate, discharging thin purulent fluid.
• Differential Diagnosis of Sporotrichoid Spread:
  • Mycobacterium marinum (fish tank granuloma).
  • Leishmania braziliensis (cutaneous leishmaniasis).
  • Nocardia brasiliensis (nocardiosis).
  • Francisella tularensis (ulceroglandular tularemia).
• Diagnostic Confirmation: Fungal culture on Sabouraud agar (demonstrating thermal dimorphism). Histopathology reveals mixed suppurative and granulomatous dermatitis with microabscesses. Yeast forms are often sparse, occasionally surrounded by radiating eosinophilic proteinaceous deposits known as asteroid bodies (Splendore-Hoeppli phenomenon).
• Treatment: Oral Itraconazole (200 mg once daily for 3 to 6 months, continued for 4 weeks after complete clinical resolution) is the established first-line treatment of choice. Intravenous Amphotericin B is reserved for severe pulmonary or systemic disease.

2. Mycetoma (Madura Foot)

• Definition & Geography: A chronic, indolent, debilitating, destructive granulomatous inflammatory infection of the subcutaneous tissue, deep fascia, and bone. Endemic in tropical and subtropical regions between latitudes 15°S and 30°N (the "mycetoma belt": Sudan, Somalia, India, Mexico).
• Pathognomonic Clinical Triad:
  1. Massive, localized, firm, non-pitting subcutaneous swelling and tumefaction.
  2. Multiple interconnected sinus tracts discharging purulent and serosanguinous fluid to the cutaneous surface.
  3. Presence of visible, macroscopic grains or granules extruded in the discharging sinus exudate (representing dense compacted colonies of the causal organism).
• Etiological Classification:
  • Actinomycetoma (Bacterial Mycetoma, ~60%): Caused by aerobic filamentous actinomycetes: Nocardia brasiliensis, Actinomadura madurae, Streptomyces somaliensis. Grains are typically white, yellow, or red. Responsive to prolonged antibacterial medical therapy alone: the Welsh regimen (intravenous amikacin combined with oral trimethoprim-sulfamethoxazole [TMP-SMX] in cycles for 6 to 12 months).
  • Eumycetoma (True Fungal Mycetoma, ~40%): Caused by true fungi: Madurella mycetomatis (producing diagnostic black grains), Falciformispora senegalensis, and Scedosporium apiospermum (pale grains). Eumycetoma responds poorly to medical antifungal therapy alone. Standard management requires prolonged high-dose oral Itraconazole (400 mg daily for 6 to 12 months) combined with wide, conservative surgical debridement or bone excision to achieve local cure and prevent amputation.

3. Chromoblastomycosis

• Etiology: Transcutaneous traumatic inoculation of dematiaceous (pigmented, dark-walled) saprophytic fungi that synthesize dihydroxynaphthalene (DHN) melanin into their cell walls: Fonsecaea pedrosoi (most common worldwide), Cladophialophora carrionii, and Phialophora verrucosa.
• Clinical Presentation: Typically affects agricultural workers and rural laborers walking barefoot. Begins as a solitary pink papule on an extremity (foot, lower leg) that slowly expands over months and years into hyperkeratotic, verrucous, crusted, cauliflower-like vegetative plaques. Lesions display dark, cayenne-pepper-like surface dots representing transepidermal elimination of pigmented fungal elements. In chronic, long-standing, untreated disease, secondary scarring and persistent inflammation predispose to cutaneous squamous cell carcinoma transformation.
• Pathognomonic Diagnostic Hallmark: Direct KOH mount or histopathological H&E section reveals muriform cells (also designated Medlar bodies, sclerotic cells, or "copper pennies"). These are thick-walled, chestnut-brown, round-to-polyhedral cells (5–12 µm in diameter) that divide characteristically by internal cross-septation (internal cleavage planes) rather than by budding. They reside within dermal microabscesses or multinucleated giant cells.
• Therapeutic Approach: Exceptionally refractory to treatment. Prolonged oral Itraconazole (200–400 mg daily) or Terbinafine (500 mg daily) for 6 to 12+ months, frequently combined with physical modalities including local cryotherapy with liquid nitrogen, surgical excision, or local heat application.