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Recalcitrant Dermatophytosis and Management of Different Types of Tinea

I. Recalcitrant Dermatophytosis

Definition

• Persistence or relapse after ≥2 standard courses of treatment
• Progression or enlargement of lesions during therapy
• Minimal or no mycological clearance on follow-up KOH/culture

Causes of Recalcitrance

Trichophyton indotineae — The Key Emerging Pathogen

• Widespread large annular lesions
• Terbinafine resistance (squalene epoxidase gene mutations — SQLE mutations at codons Leu393Phe, Ala448Thr, Phe397Leu)
• Epidemic spread in the Indian subcontinent and globally
• Often presents as highly inflammatory tinea corporis/cruris

• Antifungal susceptibility testing (EUCAST/CLSI MIC)
• Itraconazole 200–400 mg/day × 4–8 weeks (drug of choice for terbinafine-resistant cases)
• Voriconazole or posaconazole for severe/disseminated cases
• Combination topical therapy (luliconazole, efinaconazole)
• Avoid combination steroid-antifungal preparations
• Screen and treat household contacts
• Stop immunosuppressants where possible

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II. Management of Different Types of Tinea Causing Dermatophytosis

1. Tinea Capitis (Scalp Ringworm)

• Oral therapy is mandatory (scalp and hair follicles inaccessible to topical agents alone)
• Griseofulvin (drug of choice for Microsporum): 10–15 mg/kg/day microsize × 6–8 weeks (ultramicrosize: 5–10 mg/kg/day)
• Terbinafine (preferred for Trichophyton): Children — weight-based (10–20 kg: 62.5 mg/day; 20–40 kg: 125 mg/day; >40 kg: 250 mg/day) × 4–6 weeks
• Itraconazole: 3–5 mg/kg/day × 4–6 weeks (pulsed regimen acceptable)
• Fluconazole: 6 mg/kg/day × 3–6 weeks
• Adjuvant topical: 2% ketoconazole or 1% selenium sulfide shampoo twice weekly — reduces spore count and prevents family spread
• Kerion: Add oral prednisolone 1 mg/kg × 2 weeks; treat secondary bacterial infection; avoid incision and drainage

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2. Tinea Corporis (Ringworm of the Body)

• Allylamines: Terbinafine 1%, Naftifine 1% — applied BD × 2–4 weeks
• Azoles: Clotrimazole 1%, Miconazole 2%, Luliconazole 1% (newer, once daily)
• Ciclopirox olamine 0.77% — broad spectrum, apply BD × 4 weeks
• Apply cream at least 2 cm beyond visible lesion margins

• Terbinafine 250 mg/day × 2–4 weeks
• Itraconazole 100–200 mg/day × 2–4 weeks OR pulse (200 mg BD × 1 week/month × 2 pulses)
• Fluconazole 150–300 mg/week × 2–4 weeks

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3. Tinea Cruris (Jock Itch / Eczema Marginatum)

• Topical: Azoles (clotrimazole, miconazole, ketoconazole) or allylamines (terbinafine) BD × 2–4 weeks; luliconazole 1% OD × 1 week
• Systemic: Terbinafine 250 mg/day × 2 weeks; itraconazole 100 mg/day × 2 weeks
• General measures: Weight reduction, loose-fitting cotton clothing, drying powder (plain talc), treat concomitant tinea pedis/unguium

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4. Tinea Pedis (Athlete's Foot)

1. Interdigital (commonest): Maceration, scaling in 3rd/4th web space
2. Moccasin/hyperkeratotic: Diffuse scaling, plantar, chronic — most recalcitrant
3. Vesiculobullous/inflammatory: Vesicles on instep
4. Ulcerative: Bacterial co-infection common

• Topical (mild-moderate): Terbinafine 1% cream BD × 1–2 weeks; ciclopirox, clotrimazole × 4 weeks
• Oral (moccasin type, widespread, associated onychomycosis):
  • Terbinafine 250 mg/day × 2–6 weeks (moccasin type needs 6 weeks)
  • Itraconazole 200 mg BD × 1 week or 100 mg/day × 4 weeks
  • Fluconazole 150–300 mg/week × 4–6 weeks
• Bacterial superinfection: Topical/systemic antibacterials; dilute acetic acid soaks
• Vesiculobullous: Short-course topical corticosteroid for symptomatic relief alongside antifungal

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5. Tinea Unguium (Onychomycosis)

• Amorolfine 5% nail lacquer (once weekly × 6–12 months)
• Ciclopirox 8% nail lacquer (daily × 6–12 months)
• Efinaconazole 10% solution; Tavaborole 5% solution

• Combination oral + topical
• Chemical nail avulsion (40% urea paste) or surgical avulsion before oral therapy
• Check for non-dermatophyte mold infection (require different treatment)

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6. Tinea Barbae (Tinea Sycosis)

• Oral antifungals mandatory — topical ineffective in follicular infection
• Terbinafine 250 mg/day × 4 weeks
• Itraconazole 200 mg/day × 2–4 weeks
• Griseofulvin 500–1000 mg/day × 4–8 weeks
• Depilate affected area; treat concomitant bacterial superinfection

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Summary Table: Preferred Systemic Agents

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1. Topical therapy alone is never adequate for tinea capitis, barbae, or nail disease
2. Avoid topical steroid-antifungal combinations (irrational FDCs) — major cause of recalcitrant dermatophytosis
3. T. indotineae terbinafine resistance is a current epidemic; itraconazole is preferred
4. Treat predisposing factors (diabetes, immunosuppression, hyperhidrosis) simultaneously
5. Family and close contact screening is essential to prevent reinfection

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Complications of Psoriasis and Management of Severe Forms

PART A: COMPLICATIONS OF PSORIASIS

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1. Psoriatic Arthritis (PsA)

• Occurs in 10–30% of psoriasis patients
• Most common systemic complication
• Five clinical patterns:
  1. Asymmetric oligoarthritis (most common) — DIP joint involvement, "sausage digits" (dactylitis)
  2. Symmetric polyarthritis (resembles RA, RF-negative)
  3. DIP joint predominant
  4. Spondyloarthropathy (sacroiliitis, ankylosing spondylitis)
  5. Arthritis mutilans — severe destructive, "telescoping fingers"
• Nail disease (subungual hyperkeratosis, pitting, onycholysis) is a prognostic marker for arthritis development
• HLA-B27 association in spondylitic form

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2. Cardiovascular Complications

• Psoriasis is an independent risk factor for myocardial infarction, stroke, and peripheral vascular disease
• Chronic inflammation → endothelial dysfunction → accelerated atherogenesis
• Risk proportional to psoriasis severity (severe psoriasis = 3× increased MI risk)
• TNF-α inhibitors and methotrexate have been associated with decreased MI rates in treated patients
• Screen all patients: BP, lipid profile, fasting glucose, BMI

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3. Metabolic Syndrome

• Constellation of: obesity, hypertension, dyslipidemia, insulin resistance/type 2 DM
• Prevalence of metabolic syndrome 2–3× higher in psoriasis vs. general population
• Shared pathogenesis: TNF-α and IL-6 promote insulin resistance and adipogenesis
• Non-alcoholic fatty liver disease (NAFLD) also increased — relevant for methotrexate hepatotoxicity monitoring

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4. Erythrodermic Psoriasis

• Life-threatening complication — generalized erythema and scaling over >90% body surface
• Precipitants: abrupt withdrawal of systemic corticosteroids, overuse of tar/anthralin, phototherapy burns, infections
• Complications:
  • Loss of thermoregulation → hypothermia or hyperthermia
  • High-output cardiac failure (increased skin blood flow)
  • Hypoalbuminemia, electrolyte imbalances
  • Protein-losing enteropathy, dehydration
  • Sepsis from loss of skin barrier
  • Acute respiratory distress syndrome (ARDS)

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5. Generalized Pustular Psoriasis (von Zumbusch)

• Sudden onset of lakes of sterile pus on erythematous skin; systemic toxicity
• Complications: fever, hypocalcemia, cachexia, hepatitis, pneumonia, congestive heart failure, ARDS, sepsis
• Provoked by: steroid withdrawal, iodides, coal tar, terbinafine, minocycline, hydroxychloroquine

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6. Psychiatric and Psychosocial Complications

• Depression (prevalence ~25%): chronic visible skin disease + social stigma
• Anxiety, social isolation, occupational impairment
• Significant reduction in quality of life (DLQI scores comparable to heart failure, diabetes)
• Increased suicidal ideation — screen using PHQ-9 and DLQI

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7. Ocular Complications

• Conjunctivitis, blepharitis, uveitis (especially in PsA with axial involvement)
• Corneal ulcers in severe cases

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8. Iatrogenic Complications

• PUVA-related: photocarcinogenesis (SCC, melanoma), photo-aging, cataracts
• Methotrexate: hepatic fibrosis/cirrhosis, myelosuppression, pulmonary fibrosis
• Cyclosporine: nephrotoxicity, hypertension
• Biologics: serious infections, tuberculosis reactivation, demyelination, malignancy (lymphoma risk remains debated)

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9. Lymphoma

• Increased incidence of T-cell lymphoma (CTCL/PTCL) and some B-cell lymphomas
• Causation vs. shared inflammatory milieu remains debated; severe psoriasis more affected

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PART B: MANAGEMENT OF SEVERE PSORIASIS

Definition of Severe Psoriasis

• PASI (Psoriasis Area Severity Index) ≥10
• BSA (Body Surface Area) ≥10%
• DLQI >10 (significant quality of life impairment)
• Special sites: face, palms/soles, genitalia, nails — even limited BSA = severe
• Erythrodermic, generalized pustular, and psoriatic arthritis subtypes

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Step 1: General Measures

• Identify and eliminate trigger factors: infections (streptococcal), drugs (lithium, beta-blockers, NSAIDs, antimalarials, ACE inhibitors), stress, alcohol, smoking
• Emollients to reduce scaling and maintain skin barrier
• Screen and manage comorbidities (BP, glucose, lipids, depression)
• Avoid abrupt withdrawal of any systemic therapy

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Step 2: Phototherapy

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Step 3: Conventional Systemic Agents

A. Methotrexate (MTX)

• First-line systemic agent for moderate-severe plaque psoriasis, PSA
• Mechanism: inhibits dihydrofolate reductase → antiproliferative + anti-inflammatory
• Dose: 7.5–25 mg/week (oral or SC); folic acid 5 mg/week supplementation
• Monitor: LFTs, CBC, renal function (monthly initially)
• Contraindications: pregnancy (teratogenic — Category X), hepatic disease, renal impairment, immunodeficiency
• Liver biopsy historically at cumulative dose 1–1.5 g; now replaced by FibroScan + serum procollagen III
• FDA-approved for psoriatic arthritis

B. Cyclosporine

• Rapid-acting — drug of choice for acute erythrodermic psoriasis, acute pustular flares
• Mechanism: calcineurin inhibitor → suppresses T-cell activation (IL-2 inhibition)
• Dose: 2.5–5 mg/kg/day; maximum 5 mg/kg/day
• Duration: limit to 1–2 years continuous to minimize nephrotoxicity
• Monitor: BP, serum creatinine, uric acid, lipids (monthly)
• Contraindications: uncontrolled hypertension, renal impairment, malignancy, concurrent PUVA

C. Acitretin (Oral Retinoid)

• Drug of choice for pustular and erythrodermic psoriasis (especially in adults)
• Mechanism: normalizes keratinocyte differentiation
• Dose: 25–50 mg/day
• Teratogenic — pregnancy contraindicated during therapy and for 3 years after stopping
• Best combined with PUVA (Re-PUVA) or UVB
• Side effects: chelitis (nearly universal), xerosis, hypertriglyceridemia, skeletal hyperostosis (DISH), hepatotoxicity

D. Apremilast (PDE4 Inhibitor)

• Small molecule; oral; inhibits phosphodiesterase-4 → reduces cAMP breakdown → anti-inflammatory
• Dose: 30 mg BD (after titration)
• Moderate psoriasis; approved for PsA
• Advantages: no laboratory monitoring, no immunosuppression, safe in HIV
• Side effects: diarrhea, nausea, headache, depression (monitor)

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Step 4: Biologic Agents (Targeted Immunotherapy)

TNF-α Inhibitors (1st Generation Biologics)

IL-12/23 Inhibitor

• Ustekinumab: anti-p40 subunit (IL-12 + IL-23); SC 45 mg (≤100 kg) or 90 mg (>100 kg) at 0, 4 wk, then q12 weeks; excellent durability

IL-17A/F Inhibitors (Highest PASI 90/100 response rates)

• Caution: do not use in inflammatory bowel disease (IL-17 protective in gut)
• Increased risk of oral candidiasis

IL-23 Inhibitors (Selective p19 — most targeted)

• Most favorable safety profile among all biologics; no TB reactivation signal
• IL-23 inhibitors are the current preferred choice for severe chronic plaque psoriasis

IL-36R Inhibitor (GPP-specific)

• Spesolimab: approved for generalized pustular psoriasis flares (IV, single dose)

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Step 5: Management of Specific Severe Subtypes

Erythrodermic Psoriasis

1. Hospitalization — monitor vitals, fluid/electrolyte balance, temperature
2. Supportive care: emollients, warm baths, barrier nursing, treat infections, correct hypoalbuminemia, DVT prophylaxis
3. Cyclosporine (drug of choice for rapid control) 4–5 mg/kg/day
4. Methotrexate — slower onset but effective
5. Infliximab IV — rapid biological option
6. Acitretin — for pustular erythroderma
7. Avoid systemic corticosteroids — risk of rebound pustulation on withdrawal

Generalized Pustular Psoriasis (von Zumbusch)

1. Hospitalization, ICU if systemic complications
2. Acitretin — drug of choice (rapid pustule resolution)
3. Cyclosporine — effective alternative
4. Methotrexate — slower but effective
5. Spesolimab (anti-IL-36R) — FDA/EMA approved for GPP flares; 900 mg IV single dose
6. Spesolimab subcutaneous for maintenance (imsidolimab also in trials)
7. Dapsone 50–100 mg/day — useful adjunct

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Summary: Treatment Algorithm for Severe Psoriasis

Severe Psoriasis (PASI ≥10, DLQI >10)
        │
        ▼
Phototherapy (NBUVB / PUVA) ± Topicals
        │ Failure
        ▼
Conventional Systemics (MTX / Cyclosporine / Acitretin)
        │ Failure / Contraindication / Intolerance
        ▼
Biologic Therapy
  ├── IL-23 inhibitors (guselkumab, risankizumab) — preferred
  ├── IL-17 inhibitors (secukinumab, ixekizumab) — highest PASI response
  └── TNF inhibitors (adalimumab, infliximab) — if arthritis predominant

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Key Examination Points

1. PASI ≥10 + DLQI >10 = moderate-severe; biologics indicated after 2 conventional failures
2. Cyclosporine = drug of choice for acute erythrodermic/pustular crises (fastest action)
3. Acitretin = drug of choice for pustular psoriasis (generalized); teratogenic for 3 years post-treatment
4. IL-17 inhibitors achieve highest PASI 90/100 rates; IL-23 inhibitors have best durability and safety
5. Spesolimab (IL-36R inhibitor) is the first targeted therapy approved specifically for GPP
6. Never use systemic corticosteroids in plaque psoriasis — risk of life-threatening pustular rebound
7. Screen for TB, hepatitis B/C, HIV before all biologics; isoniazid prophylaxis for latent TB