Topical antipsoriatics

Definition and Clinical Relevance

Topical antipsoriatics are pharmacological agents formulated for dermal application, specifically used to manage and alleviate symptoms of psoriasis. Psoriasis is a chronic, immune-mediated inflammatory skin disorder characterized by hyperproliferation and abnormal differentiation of keratinocytes, leading to scaly, erythematous plaques most commonly affecting the elbows, knees, scalp, and lower back. Topical agents are considered first-line treatment for mild to moderate psoriasis, and they may also serve as adjunctive therapy in more extensive cases. These agents act directly at the site of pathology, aiming to reduce inflammation, normalize keratinocyte proliferation, alleviate pruritus, and enhance cosmetic appearance.

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Pharmacological Categories of Topical Antipsoriatics

1. Topical Corticosteroids (Potency-based)

   • Mechanism: Anti-inflammatory, antiproliferative, immunosuppressive effects

   • Examples:

     • Hydrocortisone (low potency)

     • Betamethasone dipropionate (high potency)

     • Clobetasol propionate (very high potency)

   • Usage: Often prescribed for flare control due to rapid effect. Used alone or in combination.

   • Caution: Long-term use is associated with skin atrophy, striae, telangiectasia, and tachyphylaxis.

2. Vitamin D Analogues

   • Mechanism: Regulate keratinocyte proliferation and differentiation by binding to vitamin D receptors, also exert mild immunomodulatory effects.

   • Examples:

     • Calcipotriol (calcipotriene)

     • Calcitriol

     • Tacalcitol

   • Benefits: Suitable for long-term use with favorable safety profile.

   • Limitations: May cause local irritation; not to be applied on the face.

3. Coal Tar Preparations

   • Mechanism: Antiproliferative, anti-inflammatory, and anti-pruritic properties.

   • Examples:

     • Coal tar solution

     • Coal tar ointments or shampoos

   • Indications: Particularly effective for scalp and plaque psoriasis.

   • Drawbacks: Strong odor, staining of clothing, photosensitivity.

4. Dithranol (Anthralin)

   • Mechanism: Inhibits DNA synthesis and mitochondrial function in keratinocytes, reducing hyperproliferation.

   • Formulations: Often applied as short-contact therapy (5–30 minutes).

   • Limitation: Can cause severe skin irritation and staining of skin and fabrics.

5. Topical Retinoids

   • Mechanism: Normalize epidermal cell turnover and reduce inflammation.

   • Example:

     • Tazarotene

   • Indications: Plaque psoriasis, particularly effective for nail psoriasis.

   • Side Effects: Local irritation, teratogenicity (pregnancy contraindicated), photosensitivity.

6. Topical Calcineurin Inhibitors (off-label)

   • Mechanism: Inhibit T-cell activation and proinflammatory cytokine release.

   • Examples:

     • Tacrolimus

     • Pimecrolimus

   • Use: Off-label for facial and intertriginous psoriasis due to minimal risk of skin atrophy.

7. Keratolytics

   • Mechanism: Promote shedding of hyperkeratotic scales and enhance penetration of other active agents.

   • Examples:

     • Salicylic acid (most common)

     • Urea (also has moisturizing effect)

   • Caution: Avoid extensive application to prevent systemic toxicity.

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Combination Therapies in Topical Antipsoriatics

Topical combinations are employed to enhance therapeutic outcomes while minimizing adverse effects. Commonly used combinations include:

• Calcipotriol + Betamethasone dipropionate
  Rationale: Calcipotriol reduces keratinocyte hyperproliferation while betamethasone provides rapid anti-inflammatory effects.
  Example Brand: Daivobet (Dovobet in some regions)

• Salicylic acid + Topical corticosteroids
  Rationale: Salicylic acid enhances steroid penetration by breaking down scales.
  Limitation: Combined use requires monitoring for salicylate toxicity and dermal thinning.

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Pharmacokinetics and Site-specific Use

Topical drug delivery is affected by anatomical site, skin integrity, and formulation vehicle. Areas such as the face and intertriginous zones have increased permeability and are more prone to adverse effects from potent agents. Ointments generally provide better absorption and occlusion than creams or lotions.

Formulations and site recommendations:

• Ointments: Thick plaques on elbows/knees

• Lotions/sprays/foams: Hair-bearing areas like the scalp

• Creams: Intertriginous or facial areas (prefer low-potency agents)

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Adverse Effects of Topical Antipsoriatics

Each class has distinct safety profiles:

• Corticosteroids: Skin atrophy, striae, purpura, perioral dermatitis, rebound psoriasis

• Vitamin D analogues: Irritation, hypercalcemia (rare if used excessively)

• Coal tar: Folliculitis, photosensitivity, allergic reactions

• Dithranol: Severe staining, irritation, contraindicated in unstable psoriasis

• Retinoids: Erythema, peeling, teratogenicity (pregnancy contraindication)

• Calcineurin inhibitors: Transient burning sensation, theoretical cancer risk (FDA black box warning)

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Clinical Guidelines and Usage Strategy

1. Mild Psoriasis:

   • First-line: Emollients + low to medium-potency corticosteroids or vitamin D analogues

   • Alternative: Tazarotene, coal tar, or calcineurin inhibitors for sensitive areas

2. Moderate Psoriasis:

   • Combination of vitamin D analogues and corticosteroids

   • Occlusive dressings may enhance absorption

3. Special Sites:

   • Face, groin, axillae: Calcineurin inhibitors or low-potency corticosteroids

   • Scalp: Medicated shampoos (coal tar, salicylic acid), topical steroids in lotion/gel/foam

   • Nails: Tazarotene, corticosteroids under occlusion

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Generic and Brand Names of Topical Antipsoriatics

1. Calcipotriol

   • Brands: Dovonex, Psorcutan, Daivonex

2. Calcipotriol + Betamethasone dipropionate

   • Brands: Daivobet, Enstilar (foam)

3. Tazarotene

   • Brands: Tazorac, Zorac

4. Anthralin (Dithranol)

   • Brands: Dritho-Scalp, Micanol

5. Tacrolimus / Pimecrolimus

   • Brands: Protopic (Tacrolimus), Elidel (Pimecrolimus)

6. Coal Tar

   • Brands: T-Gel, Polytar, Exorex

7. Salicylic Acid

   • Found in: Keralyt, Sebcur, Diprosalic (with betamethasone)

8. Clobetasol propionate

   • Brands: Dermovate, Temovate, Clobex

9. Hydrocortisone

   • OTC and prescription formulations

10. Betamethasone dipropionate

    • Brands: Diprolene, Luxiq, Beta-Val

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Precautions and Patient Education

• Do not apply potent corticosteroids to large areas or for prolonged periods.

• Monitor calcium levels during prolonged use of vitamin D analogues.

• Advise on the proper timing and layering of topical agents if using multiple therapies.

• Ensure patient adherence through education about therapeutic expectations and side effect management.

• Use gloves or applicators to minimize fingertip exposure to agents like dithranol or tazarotene.

• Avoid UV exposure when using photosensitizing agents like coal tar or retinoids.

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Drug Interactions

• Calcipotriol: Additive hypercalcemia risk with oral calcium/vitamin D supplements.

• Topical corticosteroids: Potent steroids may suppress hypothalamic-pituitary-adrenal (HPA) axis with extensive use or with concurrent systemic steroids.

• Tazarotene: May enhance photosensitivity with concurrent use of photosensitizing drugs (e.g., tetracyclines, thiazides).

• Coal tar: Increased risk of phototoxicity when combined with UV therapy (e.g., PUVA).

• Calcineurin inhibitors: Although minimal systemic absorption, avoid concurrent immunosuppressants unless indicated by a specialist.

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Regulatory and Safety Updates

• The FDA and EMA require clear labeling on vitamin D analogues and retinoids regarding teratogenic potential and safe usage limits.

• Tacrolimus and pimecrolimus carry boxed warnings in the U.S. regarding long-term cancer risk (although controversial and based on systemic data).

• The use of tazarotene in women of childbearing age requires pregnancy testing and reliable contraception.