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Introduction

Corticosteroids are essential in the treatment plan of many skin diseases. Prednisolone is one of glucocorticoids used widely in dermatology. Prednisolone, which is intermediate‐acting, is the biologically active metabolite of prednisone. Here, we will discuss most of prednisolone indications and dosage in dermatology. Despite its importance, we should be aware of side effects and precuations of prednisolone usage.

Indications of prednisolone in dermatology

Pyoderma faciale.
Acne fulminans.
Pemphigus vulgaris.
Acne associated with congenital adrenal hyperplasia in male patients.
Bullous pemphigoid (moderate to severe cases).
Pemphigoid gestationis.
Pyoderma gangrenosum.
Life or function-threatening hemangioma.
Necrobiosis lipoidica.
Widespread cutaneous lichen planus.
Oral lichen planus.
Lichen planopilaris.
Chronic cutaneous lupus erythematosus (active).
Nail lichen planus(more than 2 nails).
Grade 2 acute graft‐versus‐host disease.
Chronic graft‐versus‐host disease( moderate or severe disease).
Papuloerythroderma of ofuji.
Severe exacerbations of atopic eczema.
Chronic urticaria.
Episodic angio‐oedema with eosinophilia.
Urticarial vasculitis (unresponsive patients).
Severe cases of erythema multiforme( debated).
Sweet syndrome.
Pyodermatitis–pyostomatitis vegetans.
Mucous membrane pemphigoid.
Anti‐p200 pemphigoid.
Epidermolysis bullosa acquisita.
Bullous systemic lupus erythematosus.
Lupus erythematosus.
Dermatomyositis.
Hailey–hailey disease.
Extensive and rapidly progressive alopecia areata.
Graham‐little syndrome.
Relapsing polychondritis.
Polymorphic light eruption.
Mixed cryoglobulinaemia.
Sjs/ten (may increase the risk of sepsis and impair re‐epithelialization ).
Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome.
Atopic eruption of pregnancy.
Polymorphic eruption of pregnancy( severe cases).
Leprosy reactions in pregnancy.
Lipschutz ulceration(large lesions).
Dissecting cellulitis of the scalp.
Eosinophilic granulomatosis with polyangiitis.
Cutaneous small‐vessel vasculitis.
Sarcoidosis.

Dosage of prednisolone in dermatology

Pyoderma faciale : prednisolone (1.0 mg/kg daily for 1 to 2 weeks). Isotretinoin was then added.
Acne fulminans :prednisolone 0.5 to 1.0 mg/kg + isotretinoin (0.5 mg/kg).
Pemphigus vulgaris : prednisolone 2 mg/kg/day plus azathioprine 2 to 2.5 mg/kg/day.
Acne associated with congenital adrenal hyperplasia in male patients : 2.5–5 mg/day.
Bullous pemphigoid (moderate to severe cases): 0.5 – 1.0 mg/kg/day.
Pemphigoid gestationis : start at a dose of 0.5–1 mg/kg/day. The common ﬂare associated with delivery usually requires a temporary increase in dosage.
Pyoderma gangrenosum : 0.5–1 g/kg.
Life- or function-threatening hemangioma : prednisolone (2 to 3 mg/kg per day) given over a mean of 1.8 months.
Widespread cutaneous lichen planus : 0.5–1 mg/kg per day until improvement (usually 4–6 weeks).
Oral lichen planus : soluble prednisolone tablet 5 mg dissolved in 15 ml water for a mouthwash swish and rinse three times daily>>oral candidiasis is the most frequent complication.
Lichen planopilaris : 1 mg/kg/day.
Chronic cutaneous lupus erythematosus (active) : 1 mg/kg.
Nail lichen planus(more than 2 nails) : 0.5–1 mg/kg/day.
Grade 2 acute graft‐versus‐host disease :1 mg/kg.
Chronic graft‐versus‐host disease( moderate or severe disease): 1 mg/kg oral for 2 weeks then tapering to 0.5 mg/kg.
Severe exacerbations of atopic eczema :0.5 mg/kg to be tapered over several weeks.
Chronic urticaria : 30–50 mg daily (prolonged use should be avoided).
Episodic angioedema with eosinophilia.
Urticarial vasculitis : (unresponsive patients): 40 mg/day or more for short‐term management.
Severe cases of erythema multiforme:30–60 mg/day, decreasing over a period of 1–4 weeks( debated).
Sweet syndrome : 0.5–1 mg/kg for 4–6 weeks.
Mucous membrane pemphigoid (for high risk patients): oral cyclophosphamide 2 mg/day plus prednisolone 1.0 mg/kg/day.
Mucous membrane pemphigoid (for low‐risk patients):oral prednisolone (0.5 mg/kg/day) with or without azathioprine 100–150 mg/day.
Anti‐p200 pemphigoid : 0.5 mg/kg/day tapering doses.
Epidermolysis bullosa acquisita : 0.5–2.0 mg/kg/day, depending on disease severity + colchicine 0.5–3.0 mg/day ± dapsone 1.5 mg/kg/day.
Bullous systemic lupus erythematosus : prednisolone 0.5–1.0 mg/kg/day (depending on disease severity) + azathioprine 2.5 mg/kg/day (with normal TPMT activity) or mycophenolates (2 g/day; 1.440 mg/day).
Dermatomyositis:( both skin and muscles ) oral prednisolone 0.5–1.0 mg/kg.
Hailey–hailey disease :oral prednisolone 20–30 mg/day; short course in acute ﬂares.
Extensive and rapidly progressive alopecia areata : oral prednisolone (starting at 40 mg/day).
Relapsing polychondritis: initial daily dose of 30 mg prednisolone can be gradually reduced.
SJS/TEN : 0.5–1 mg/kg daily for 10 days, and tapered(may increase the risk of sepsis and impair repithelialization).
Dress : 1 mg/kg/day tapering‐off period varying from 1 to 3 months.
Polymorphic eruption of pregnancy( severe cases):prednisolone starting at 40–60 mg/day and tapering to zero over a few weeks.
Leprosy reactions in pregnancy : 40–60 mg daily for 2 weeks followed by a steady reduction in the dose.
Lipschutz ulceration(large lesions) : 15–20 mg/day for 10 days.
Dissecting cellulitis of the scalp: isotretinoin (1 mg/kg daily)+ prednisolone (0.5–1 mg/kg daily) + erythromycin (500 mg four times daily).
Cutaneous small‐vessel vasculitis:30–80 mg once daily, tapered over 2–3 weeks.

Corticosteroid dose equivalent

5 mg prednisolone = 4 mg triamcinolone = 20 mg hydrocortisone = 0.75 mg dexamethasone.

Mechanism of action

Prednisolone is a glucocorticoid receptor agonist.
On binding, the corticoreceptor-ligand complex translocates itself into the cell nucleus, where it binds to many glucocorticoid response elements (GRE) in the promoter region of the target genes.
The DNA bound receptor then interacts with basic transcription factors, causing an increase or decrease in expression of specific target genes.

Effects

Anti-inflammatory effect : NFκB inhibition and AP-1 inhibition.
Anti-inflammatory effect : Phospholipase A2 inhibition >> Cyclo-oxygenase 2 inhibition (COX-2) >> ↓ prostaglandins, leukotrienes.
B-cells : with higher doses >> inhibit Ig production.
Mast cells : Inhibit degranulation, with resultant ↓ release histamine, kinins, other mediators.
Monocytes,macrophages : ↓ monocyte maturation; ↓ access to inﬂammatory sites, ↓ IL-1 and IFN-γ release.
Langerhans cells :↓ characteristic surface markers, impaired antigen processing and presentation.
Eosinophils, basophils : Reduced numbers and function both cell types, ↓ recruitment to inﬂammatory sites.
Fibroblasts :↓ production of collagen, ground substance, fbronectin and collagenase.
Angiogenesis :↓ angiogenesis in wound healing and with proliferative lesions (hemangiomas).
In autoimmune disorders: apoptosis of autoreactive T cells.
In allergic disorders : apoptosis of eosinophils.
In certain neoplastic disorders: apoptosis of malignant T cells.

Baseline Monitoring

Examination
- Blood pressure, weight.
- Height and weight plotted on a growth curve (in children).
- Ophthalmoscopic examination for cataracts.
Lab
- TB screening (strongly consider) tuberculin skin test (or IFN-γ-releasing assay), chest X-ray.
- Fasting glucose and triglycerides; potassium level.

Follow Up Monitoring

Examination(at 1 month, then at least every 2–3 months)
- Blood pressure, weight.
- Height and weight plotted on a growth curve(in children).
- History each visit for adverse effects.
- Ophthalmologic examination for cataracts and glaucoma(At least every 6 months initially; at least every 12 months long-term).
Lab (At 1 month, then at least every 3–4 months while on pharmacologic dose CS)
- Potassium levels.
- Glucose levels (fasting).
- Triglycerides (fasting).
Near time of cessation of long-term pharmacologic dose CS therapy (optional).
- AM cortisol level (or another suitable test of adrenal function or the entire HPA axis).

Side effects

Metabolic effects
- Hyperglycemia.
- Hyperlipidemia.
- Obesity.
- Hypocalcemia.
- Hypokalemic alkalosis.
- Cushingoid changes.
Cardiovascular
- Hypertension : sodium retention , vasoconstriction.
- Peripheral edema.
- Atherosclerosis.
- Congestive heart failure : ↑ sodium retention, resultant ﬂuid overload in predisposed individuals.
Hematologic
- Leukocytosis.
- Lymphopenia.
- Eosinopenia.
- Immunosuppression with increased risk of infections.
Nervous system
- Mood, personality changes.
- Psychiatric problems, psychosis.
- Seizures.
- Pseudotumor cerebri.
- Peripheral neuropathy.
- Epidural lipomatosis.
Musculoskeletal
- Osteoporosis.
- Osteonecrosis (e.g. hip).
- Growth retardation.
- Muscle atrophy.
- Myopathy.
Hypothalamic–pituitary–adrenal (HPA) axis
- Suppression.
- Withdrawal syndrome .
- Adrenal (addisonian) crisis.
Gynecologic, obstetric
- Amenorrhea.
- Fetal effects (rare adrenal insuffciency; cleft palate in animal studies).
Gastrointestinal effects
- Nausea, vomiting.
- Gastroesophageal reﬂux.
- Peptic ulcer disease.
- Intestinal perforation.
- Pancreatitis.
- Esophagitis (reﬂux or candidal)-Peptic ulcer disease : ↓ mucus production, ↑ acid production.
Ophthalmologic.
- Cataracts.
- Glaucoma.
- Infection.
- Hemorrhage.
- Exophthalmos.

Cutaneous
- Atrophy, striae, telangiectasia.
- Vascular fragility, purpura.
- Acne, acneiform eruptions.
- Hirsutism.
- Infections.

Contraindications

Absolute
- Systemic fungal infections.
- Herpes simplex keratitis.
- Hypersensitivity (primarily occurs with ACTH, occasionally noted with IV preparations).

Relative
- Cardiovascular: hypertension, CHF.
- Central nervous system: prior psychosis, severe depression.
- Gastrointestinal: active PUD, recent anastomosis.
- Infections: active TB, positive tuberculin skin test.
- Metabolic: diabetes mellitus.
- Musculoskeletal: osteoporosis.
- Ocular: cataracts, glaucoma.
- Use of live vaccines.

Interactions

Cyclosporine May Reduce Clearance Of Prednisolone.
Decreased levels of steroids: barbiturates, phenytoin, ephedrine, rifampin, cholestyramine.
Increased levels of steroids: estrogens, ketoconazole, aspirin, nonsteroidal anti-inflammatory agents, macrolides.
Decreased levels of: warfarin, vaccines, antidiabetic agents, isoniazid.
Increased levels of: cyclosporin, potassium-depleting diuretics, digitalis.
Hypokalemia: potassium-depleting diuretics, digitalis, albuterol.
Weakness in myasthenia gravis: anticholinesterase agentsand Mifepristone is contraindicated in pt on long term corticosteroids.

Pregnancy &Lactation

The safety of glucocorticoids during the first trimester of pregnancy has been debated. Slight increase in cleft lip with or without cleft palate was suggested.
Prednisolone should be used during pregnancy only if potential benefit justifies potential risk to fetus.
Prednisolone appears in human milk in minimal amounts.
For high doses, nursing should be delayed for about 4 hours after prednisone administration.

Precautions

Consider giving prednisolone at a starting dose of up to 1 mg/kg body weight daily, ideally given as a single dose in the morning.
Morning dose less likely to result in HPA axis suppression than when given at other times of day.
Long-term use associated with fluid retention and hypertension.
Development of Kaposi’s sarcoma associated with prolonged corticosteroid use.
If It is used for 10 days or longer, intraocular pressure should be routinely monitored.
Steroids should be used with caution in the presence of glaucoma. Intraocular pressure should be checked frequently.
Steroids after cataract surgery may delay healing and increase incidence of bleb formation.
Use of ocular steroids may prolong course and may exacerbate severity of many viral infections of the eye (including herpes simplex).
Patients receiving corticosteroids should avoid chickenpox or measles-infected persons if unvaccinated.
Latent tuberculosis may be reactivated (patients with positive tuberculin test should be monitored).
Suppression of hypothalamic-pituitary-adrenal axis may occur particularly in patients receiving high doses for prolonged periods or in young children; discontinuation of therapy should be done through slow taper.
A maintenance dose should not exceed 10–15 mg/day in the first trimester, as a slightly increased risk for cleft lip or cleft palate cannot be excluded.
In treating pregnancy dermatoses, corticosteroids are usually used only as a short‐term therapy (<4 weeks).
In rare cases with high‐dose therapy over many weeks, fetal growth should be monitored by ultrasound.

Drug Info

Prednisolone requires no metabolic conversion to be active, has a quicker onset of action, and has a cortisol-binding globulin affinity greater than that of prednisone.
Administration of live virus vaccines usually is not contraindicated in patients receiving corticosteroid therapy as short-term (<2 weeks) treatment, in low-to-moderate dosages, as long-term alternate-day treatment with short-acting preparations, or in maintenance of physiologic dosages (replacement therapy).
Prednisolone has intermediate mineralocorticoid activity activity.
Prednisolone is the systemic corticosteroid of choice in pregnancy.

Sources

Systemic corticosteroid
Dermatology , Edited by Jean L. Bolognia , Julie V. Schaffer , Lorenzo Cerroni Fourth edition: Elsevier, 2018, ISBN 978–0‐7020–6275–9.
Griffiths, C., Barker, J., Bleiker, T. O., Chalmers, R., & Creamer, D. (Eds.). (2016). Rook’s textbook of dermatology. John Wiley & Sons.
Lebwohl, M. G., Heymann, W. R., Berth-Jones, J., & Coulson, I. (2013). Treatment of skin disease E-Book: comprehensive therapeutic strategies. Elsevier Health Sciences.

Immunosuppressive effects of Corticosteroids

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