Topical Corticosteroids

Mechanism

Pharmacological Class and Group

Synthetic glucocorticoids formulated for topical application, classified according to their intrinsic vasoconstrictive potency into 7 classes (American system) or 4 groups (European system, from low-potency I to very high-potency IV).

Mechanism of Action

Topical corticosteroids passively diffuse through cell membranes and couple with high affinity to cytosolic glucocorticoid receptors (GR-α). The active receptor translocates to the nucleus, interacting with specific response elements and transcription factors.

Immunomodulatory and Vasoconstrictor Mechanism of Action

1. Transrepression Mechanism (Main Anti-inflammatory): The active GR complex physically binds and inactivates the proinflammatory transcription factors NF-κB (Nuclear Factor kappa B) and AP-1 (Activating Protein 1). This turns off the transcription of key interleukins involved in innate and adaptive immunity:

Topical Corticosteroids Inhibition of NF-κB ↓ IL-1, IL-2, IL-6, TNF-α and IFN-γ

2. Transactivation Mechanism (Metabolic and Barrier Effects): Stimulates the transcription of the gene for Lipocortin-1 (Annexin-A1), a protein that directly inhibits Phospholipase A2, blocking the release of arachidonic acid and the subsequent inflammatory cascade of prostaglandins and leukotrienes.

3. Topical Vasoconstrictor Effect: They induce contraction of the vasculature of the superficial dermis by enhancing sensitivity to endogenous catecholamines and stabilizing the cellular lysosomal membrane of endothelial cells, reducing the clearance of inflammatory mediators and local edema.

Indicators and dose

Clinical Indications and Off-Label Uses

• Atopic Dermatitis and Eczema (Seberrheic, Contact Allergic, Numular): First-line therapy for the rapid control of pruritic erythematous-desquamative outbreaks.
• Vulgar Psoriasis (Mild to Moderate): Reduction in the thickness of psoriatic plaques and follicular erythema, often in synergy or coformulation with calcipotriol (vitamin D analogue).
• Lichen Sclerosus and Lichen Planus: First-line management (especially very high potency formulations such as clobetasol).
• Alopecia Areata (focused): Intralesional or topical application under occlusion to attenuate the lymphocytic attack on the hair follicle.

Power and Vehicle Classification (Stoughton-Cornell)

Dosage and Clinical Adjustment

• It is prescribed by the Fingertip Unit (FTU) metric. One FTU is equivalent to the amount of cream or ointment extruded from a tube with a standard 5 mm nozzle that covers the distal phalanx of the adult index finger (approximately 0.5 g).
• One FTU is enough to safely cover an area of skin equivalent to the surface of two adult palms.
• General Outbreak Guideline: Apply once or twice a day in a very thin layer on active inflammatory lesions, not exceeding 2-4 weeks for high potencies.
• Proactive Therapy (Maintenance in Severe Atopic Dermatitis): After controlling the outbreak, apply the corticosteroid two consecutive days per week (generally Saturdays and Sundays) in the previously affected areas to prevent long-term recurrences.

Security

Absolute and Relative Contraindications

Absolute Contraindications

• Active bacterial (impetigo, cutaneous tuberculosis), fungal (ringworm, candidiasis) or viral (herpes simplex, chickenpox, molluscum contagiosum) skin infections not concomitantly treated.
• Known hypersensitivity to the corticosteroid or the vehicle (risk of allergic contact dermatitis due to excipients).

Relative Contraindications

• Rosacea or active perioral dermatitis (severe risk of acneiform rebound induction).
• Open wounds, pressure ulcers or extensive skin erosions (they delay epithelialization and healing).

Adverse Effects (ADR) and Specific Toxicity

• Very common (>10% with chronic high-potency use): Epidermal and dermal skin atrophy (due to inhibition of keratinocyte growth and suppression of collagen synthesis by fibroblasts). It manifests clinically with translucent skin "like cigarette paper", formation of irreversible purplish striae, prominent superficial telangiectasias and Bateman's purpura due to extreme capillary fragility.
• Frequent (1%-10%): Tachyphylaxis phenomenon (rapid loss of vasoconstrictor and therapeutic efficacy after continued use without rest), steroid-induced rosacea, perioral dermatitis, localized hypertrichosis.
• Rare (<0.1%): Suppression of the Hypothalamic-Pituitary-Adrenal (HPA) axis with iatrogenic Cushing's Syndrome (associated with the application of large amounts of class 1 corticosteroids on large body surfaces, especially under occlusion or in pediatrics).

Critical Toxicity: Rebound Phenomenon and Addiction to Topical Corticosteroids (TSW)

Sudden discontinuation after chronic inappropriate use of high-potency corticosteroids on the face or genitals can trigger Topical Steroid Withdrawal Syndrome (TSW):

Corticosteroid Cessation Massive Rebound Vasodilation Intense Erythema ("Red Skin Syndrome") and Hyperalgesia

It presents clinically with burning erythema with a burning sensation, acneiform papules, profuse scaling and diffuse edema. To avoid this pathology, the withdrawal of powerful corticosteroids should be strictly staggered (transition to lower potency or two-day-a-week regimens - proactive therapy) and the early introduction of topical calcineurin inhibitors should be considered.

Drug Interactions of Clinical Relevance

No serious systemic interactions have been reported for common topical use, however, concomitant use with other systemic immunosuppressants may increase the risk of severe opportunistic skin infections.

Safety in Pregnancy and Breastfeeding

• Pregnancy: Compatible with precautions. Molecules of low or moderate potency applied to small surfaces are preferred. Very high potency corticosteroids applied in large doses during pregnancy have been associated in epidemiological cohort studies with a modest increase in the risk of low birth weight due to systemic absorption.
• Breastfeeding: Compatible. The mother should be instructed not to apply the corticosteroid to the nipple or breast areola just before feeding to prevent the infant from ingesting the drug directly.