Glucocorticoids

Pathophysiology and Glucocorticoid Receptor Pharmacology

How the GR Works: Transrepression vs. Transactivation

Free glucocorticoid diffuses across the cell membrane and binds to the GRα receptor in the cytoplasm. This releases chaperone proteins (HSP90), and the GC-GR complex then moves into the nucleus:

• Transrepression (the main anti-inflammatory effect): the GC-GR complex directly blocks the transcription factors NF-κB and AP-1. This prevents transcription of a wide range of pro-inflammatory cytokines (IL-1β, IL-2, IL-6, TNF-α), chemokines and the enzyme COX-2, producing the desired anti-inflammatory and immunosuppressive effect.
• Transactivation (the main source of side effects): the GC-GR complex binds directly to glucocorticoid response elements (GREs) on DNA and switches on production of lipocortin-1 (annexin A1), which inhibits phospholipase A2 and so blocks the release of arachidonic acid. The same mechanism, however, also activates metabolic pathways that raise blood sugar, weaken bone, thin the epidermis and suppress collagen synthesis.

Antiproliferative and Vasoconstrictive Effects (Vasoconstriction Assay)

• Slowing keratinocyte and fibroblast growth: glucocorticoids inhibit DNA synthesis and cell division in keratinocytes, shrinking psoriasis plaques and hyperkeratotic patches. They also reduce production of type I and III collagen by fibroblasts, which is why they can thin the dermis.
• Skin vasoconstriction: glucocorticoids make small vessels more responsive to vasoconstricting amines (noradrenaline), reduce vessel leakiness, and lessen redness and tissue swelling. The strength of this blanching effect (the Stoughton-McKenzie assay) is the classic basis for ranking the potency of topical steroids.

Routes of Glucocorticoid Use in Dermatology

Topical Corticosteroids (TCS)

Topical steroids are ranked in 7 potency classes (the US classification, based on the Stoughton-McKenzie vasoconstrictor assay), from class 1 (superpotent, e.g. clobetasol propionate 0.05%) to class 7 (low potency, e.g. hydrocortisone 1%).

• Indications: atopic dermatitis, contact dermatitis, urticaria, lichen planus and plaque psoriasis.
• Principles: use potent steroids for short courses (7–14 days) on thick skin (palms, soles, lichenified plaques); use only low- or mid-potency steroids on thin skin (face, skin folds, genitals).

Intralesional Corticosteroid Injection (IL)

A steroid suspension is injected directly into the dermis or subcutis, achieving a high local concentration without significant systemic side effects.

• Preferred agent: triamcinolone acetonide (TAC), diluted to suit the condition:
  • Keloids / hypertrophic scars: 10–40 mg/mL
  • Lichen simplex chronicus / thick plaque psoriasis: 5–10 mg/mL
  • Alopecia areata / nodulocystic acne: 2.5–5 mg/mL

Systemic Glucocorticoids

Given by mouth or intravenously for severe, life-threatening or widespread skin disease.

• Indications include pemphigus vulgaris, bullous pemphigoid, early Stevens-Johnson syndrome (SJS) / toxic epidermal necrolysis (TEN), erythroderma (exfoliative dermatitis), and grade II–III anaphylaxis.

Side Effects, Complications and Risk Management

Local Complications

• Skin atrophy and telangiectasia: loss of dermal collagen leaves the skin thin and shiny like tissue paper, with visible spider-like vessels and permanent stretch marks (striae).
• Perioral dermatitis and steroid acne: crops of tiny pustules around the mouth or on the back and chest, caused by overgrowth of follicular bacteria.
• Topical steroid withdrawal (TSW): develops when topical steroids are stopped after a period of overuse; the skin flares bright red, burns, weeps and itches intensely (red burning skin syndrome).

Systemic Complications

• HPA axis suppression and adrenal crisis: prednisolone above 7.5 mg/day for more than 3 weeks can cause the adrenal cortex to atrophy. Stopping abruptly can then trigger acute adrenal insufficiency (low blood pressure, circulatory collapse).
• Drug-induced Cushing syndrome: central obesity, a round "moon face", a buffalo hump, high blood pressure, steroid-induced diabetes, and osteoporosis with fragility fractures.

Our Tapering Protocol at Haute-Derma

Principles of Systemic Tapering

• After high-dose induction (prednisolone 1–2 mg/kg/day), once symptoms are more than 80% controlled:
  • Reduce the dose by 10–20% every 7–14 days until the physiologic dose (7.5 mg/day) is reached.
  • Below 7.5 mg/day, taper slowly by 1 mg every 2–4 weeks, checking an 8 a.m. serum cortisol to assess recovery of the HPA axis.

Topical Step-Down Therapy

• Switch from a superpotent steroid (class 1) to a mid- or low-potency steroid (classes 4–6) after 7–14 days.
• Move to proactive maintenance (prophylactic intermittent therapy): apply the steroid 2 days a week (Saturday and Sunday) to previously affected skin, and on the other days use a calcineurin inhibitor (tacrolimus 0.1%) together with a ceramide repair cream.

Repairing Skin Damage

• Treating atrophy and telangiectasia: IPL or pulsed dye laser (PDL 595 nm) to clear dilated vessels, combined with very low-energy fractional CO2 laser to stimulate fibroblasts to rebuild dermal collagen.
• Managing TSW and perioral dermatitis: stop corticosteroids completely; prescribe oral doxycycline 100 mg/day for 4–8 weeks together with topical tacrolimus 0.03% and soothing yellow-light Bio-Light therapy.