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SYSTEMIC CORTICOSTEROIDS IN DERMATOLOGY

A Comprehensive Resident's Reference

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TABLE OF CONTENTS

1. Historical Background
2. Classification and Pharmacology
3. Mechanism of Action
4. HPA Axis - The Foundation
5. Pharmacokinetics
6. Dermatologic Indications
7. Dosing Strategies
8. Routes of Administration
9. Adverse Effects - Complete Catalogue
10. Monitoring Guidelines
11. Drug Interactions
12. Special Populations
13. Steroid Tapering and Withdrawal
14. Pulse IV Corticosteroid Therapy
15. Steroid-Sparing Strategies
16. Key Tables and Figures
17. Viva Voce Questions & Answers
18. Quiz with Answers

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1. HISTORICAL BACKGROUND

Source: Wolverton SE. Comprehensive Dermatologic Drug Therapy, 3rd Ed., Chapter 12

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2. CLASSIFICATION AND PHARMACOLOGY

2a. Structural Features

• A double bond at the 4,5 position
• A ketone group at position 3
• Activity correlates with glucocorticoid and anti-inflammatory potency

2b. Key Pharmacology Table

Source: Wolverton, Table 12-1; Andrews' Diseases of the Skin, 9780323547536

• Short-acting (8-12 hrs): Hydrocortisone, cortisone
• Intermediate-acting (12-36 hrs): Prednisone, prednisolone, methylprednisolone, triamcinolone
• Long-acting (36-54 hrs): Dexamethasone, betamethasone

• Prednisone, Prednisolone, Methylprednisolone = Intermediate
• Triamcinolone = Intermediate
• Dexamethasone, Betamethasone = Long-acting

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3. MECHANISM OF ACTION

3a. Genomic (Classical) Pathway

CS enters cell → binds cytoplasmic glucocorticoid receptor (GCR)
                        ↓
         CS-GCR complex translocates to nucleus
                        ↓
         Binds Glucocorticoid Response Elements (GREs) on DNA
                        ↓
         Induces transcription of anti-inflammatory proteins
         (annexin-1/lipocortin-1, IκB, IL-10, IL-1RA)
                 OR
         Represses transcription of pro-inflammatory genes

3b. Key Transcription Factors Inhibited

NFκB Pathway

• Normally: NFκB is bound by IκB (inhibitor κB) - inactive
• Activation signals degrade IκB → free NFκB translocates to nucleus → induces:
  • "Immunoawakening" cytokines: IL-1β, TNF-α
  • Immunomodulatory cytokines: IL-2, IL-8
  • Growth factors: G-CSF, GM-CSF
  • Adhesion molecules: ICAM-1, E-selectin
  • Receptors: IL-2 receptor
  • Proinflammatory enzymes: COX-2, phospholipase A₂

1. CS-GCR complex → increased IκB formation → NFκB bound/inactivated
2. CS-GCR complex directly binds NFκB → inhibition

AP-1 Pathway

• AP-1 = c-jun homodimers or c-jun/c-fos heterodimers
• CS inhibit AP-1 activation and DNA binding
• Overlapping inflammatory genes with NFκB
• Combined NFκB + AP-1 inhibition = dramatic reduction in inflammatory mediators

Source: Wolverton, pp.147-148 (NF-κB mechanism diagram, Figure 12-2)

3c. Non-Genomic Pathway

• Occurs within seconds to minutes (too fast for gene transcription)
• Direct membrane receptor effects
• Suppression of ion channels
• Important for high-dose pulse therapy effects

3d. Corticosteroid-Induced Apoptosis

• T lymphocytes - important in autoimmune bullous diseases, CTCL, eosinophilic disorders
• Eosinophils - urticaria, atopic dermatitis, eosinophilic dermatoses
• Mast cells - urticaria, mastocytosis
• Langerhans cells - relevant in contact dermatitis, atopic dermatitis

Source: Wolverton, Chapter 12, Q12-2

3e. Anti-inflammatory and Immunosuppressive Effects

Source: Wolverton, Table 12-2

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4. HPA AXIS - THE FOUNDATION

HPA Axis in a Nutshell

Hypothalamus
     ↓ CRF (Corticotropin-Releasing Factor)
     [also released by cerebral cortex & limbic system via acetylcholine/serotonin]
Anterior Pituitary
     ↓ ACTH (from prohormone pro-ACTH/endorphin)
     [~10 bursts/day, highest frequency = early morning]
Adrenal Cortex - Zona Fasciculata
     ↓ CORTISOL (negative feedback to hypothalamus and pituitary)
     [ACTH also stimulates adrenal androgen synthesis]
     [ACTH does NOT regulate aldosterone - mineralocorticoid]

1. Diurnal rhythm (circadian) - highest 6-8 AM, lowest midnight
2. Stress response (surgical, infection, trauma, emotional)
3. Negative feedback (cortisol → suppresses CRF and ACTH)

Source: Wolverton, Box 12-1

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5. PHARMACOKINETICS

Absorption

• Oral CS have good GI absorption (bioavailability ~80% for prednisolone)
• Food may slow but does not prevent absorption
• IM depot preparations (e.g., triamcinolone acetonide): slow release over weeks

Distribution

• CS are widely distributed to most body tissues
• Bound to transcortin (corticosteroid-binding globulin, CBG) and albumin in plasma
• Only free fraction is biologically active
• Prolonged CS therapy increases free fraction (CBG saturated)
• Exception: Prednisone is NOT well distributed into fetal tissue (prednisone preferred over dexamethasone in pregnancy when treating maternal condition)

Metabolism

• Prednisone and cortisone are PRODRUGS - require hepatic conversion by 11β-hydroxysteroid dehydrogenase to active forms:
  • Cortisone → Cortisol (hydrocortisone) - active
  • Prednisone → Prednisolone - active
• In severe liver disease: Use prednisolone directly (not prednisone)
• Reduction at 4,5 double bond: hepatic and extrahepatic → inactive substance
• 3-ketone → 3-hydroxyl (tetrahydrocortisol): liver only
• Metabolites conjugated with sulfate or glucuronic acid → water-soluble → renal excretion

Plasma Half-Life vs. Biologic Activity

• Plasma half-life does NOT correlate with duration of biologic activity
• More important = duration of ACTH suppression after a single dose
• Dexamethasone: plasma t½ ~3.5 hrs BUT suppresses ACTH for 36-54 hrs

Source: Wolverton, pp.144-145; Table 12-1

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6. DERMATOLOGIC INDICATIONS

6a. Established Indications (Box 12-2, Wolverton)

• Pemphigus vulgaris - cornerstone of therapy
• Bullous pemphigoid
• Cicatricial pemphigoid
• Linear IgA bullous dermatosis
• Epidermolysis bullosa acquisita

• Severe atopic dermatitis (short courses)
• Contact dermatitis (acute severe)
• Generalized exfoliative dermatitis/erythroderma
• Erythema multiforme major/Stevens-Johnson syndrome (controversial)
• Lichen planus (severe/erosive)

• Dermatomyositis (primary therapy)
• Systemic lupus erythematosus (cutaneous manifestations + systemic)
• Systemic sclerosis (selected cases)

• Pyoderma gangrenosum (first-line)
• Sweet's syndrome (first-line)
• Behçet disease

• Acute severe urticaria/angioedema
• Chronic refractory urticaria

• Leukocytoclastic vasculitis (systemic involvement)
• Wegener's granulomatosis, PAN (with other agents)
• Urticarial vasculitis

• Alopecia areata (systemic - controversial for long-term use)

• Sarcoidosis (first-line for systemic disease)
• Pityriasis rubra pilaris
• Toxic epidermal necrolysis (early and controversial)
• Keloids (IL triamcinolone)
• Androgen-excess disorders of adrenal origin

Source: Wolverton Box 12-2; Fitzpatrick's Dermatology (sarcoidosis, pp.610); Andrews' Diseases of the Skin, p.160

6b. Disease-Specific Dosing

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7. DOSING STRATEGIES

7a. Dose Level Definitions (Wolverton Table 12-5)

7b. Dosing Philosophies

• Attack: quickly control the disease with adequate doses
• Retreat: taper as rapidly as disease allows
• Goal: attain physiologic or alternate-day doses within 1-2 months

• Rationale: HPA suppression requires daily dosing; ADT allows recovery on "off" day
• Use only short-acting or intermediate-acting CS (NOT dexamethasone or betamethasone)
• Administer the entire dose in the MORNING (matches diurnal peak)
• Anti-inflammatory effect maintained over 48-hour period
• Reduces HPA suppression, growth suppression in children, Cushingoid changes
• Less effective for severe bullous disease

• Mimics diurnal rhythm
• Minimizes HPA suppression compared to divided doses

• Maximum anti-inflammatory effect
• Maximum HPA suppression
• Reserved for acute, severe, rapidly progressing disease

Source: Wolverton, pp.155-158; Reichling and Kligman 1961 cited in Wolverton Ch.12

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8. ROUTES OF ADMINISTRATION

8a. Oral vs. Intramuscular (IM) Comparison (Wolverton Table 12-6)

Key Point: IM injections are NOT a safer delivery method than oral administration (Andrews' Diseases of the Skin, p.159)

8b. Intravenous Pulse Therapy

• Methylprednisolone: 500-1000 mg/day (or up to 15 mg/kg/day) for 3-5 days
• Rapid anti-inflammatory effect
• Lower cumulative dose than equivalent oral therapy
• Used for: pemphigus vulgaris (refractory), bullous pemphigoid, Sweet's syndrome, urticarial vasculitis, refractory alopecia areata
• Risks: sudden cardiac death (arrhythmia from electrolyte shifts), anaphylaxis, atrial fibrillation
• Requires cardiac monitoring + daily electrolytes + glucose during infusion

8c. Intralesional

• Triamcinolone acetonide: 2.5-10 mg/mL (diluted with saline or lidocaine)
• Keloids, hypertrophic scars, alopecia areata, discoid lupus, cystic acne, granuloma annulare
• Local adverse effects: atrophy, hypopigmentation, telangiectasia

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9. ADVERSE EFFECTS - COMPLETE CATALOGUE

9a. FIGURE - Overview of Systemic Steroid Side Effects

                    SYSTEMIC CORTICOSTEROID ADVERSE EFFECTS
                    ========================================

    ENDOCRINE/METABOLIC          MUSCULOSKELETAL          CARDIOVASCULAR
    ┌─────────────────────┐      ┌─────────────┐          ┌─────────────┐
    │ HPA suppression     │      │ Osteoporosis│          │Hypertension │
    │ Cushing's syndrome  │      │ AVN (hip!)  │          │Dyslipidemia │
    │ DM/hyperglycemia    │      │ Myopathy    │          │Atherosclerosis│
    │ Dyslipidemia        │      │ Growth ↓    │          └─────────────┘
    └─────────────────────┘      │ (children)  │
                                 └─────────────┘
    OCULAR                       GASTROINTESTINAL          INFECTIOUS
    ┌─────────────────────┐      ┌─────────────┐          ┌─────────────┐
    │ PSC cataract        │      │ PUD/ulcer   │          │ Bacterial   │
    │ Glaucoma            │      │ GI bleed    │          │ Fungal      │
    │ CSCR                │      │ Pancreatitis│          │ Viral (HZV) │
    └─────────────────────┘      └─────────────┘          │ PCP (rare) │
                                                          └─────────────┘
    CUTANEOUS                    NEUROPSYCHIATRIC          RENAL/FLUID
    ┌─────────────────────┐      ┌─────────────┐          ┌─────────────┐
    │ Skin atrophy/striae │      │ Mood changes│          │ Na/fluid    │
    │ Steroid acne        │      │ Insomnia    │          │ retention   │
    │ Cushingoid habitus  │      │ Psychosis   │          │ Hypokalemia │
    │ Hirsutism           │      │ Depression  │          └─────────────┘
    │ Impaired healing    │      └─────────────┘
    │ Purpura/ecchymosis  │
    └─────────────────────┘

9b. HPA Axis Adverse Effects

• Risk begins with >7.5 mg/day prednisone for >3-4 weeks
• Takes 6-12 months for full HPA recovery after stopping long-term CS
• Patients can present with "adrenal crisis" during surgical stress, severe illness, trauma
• Management: stress-dose steroids (hydrocortisone 100 mg IV q8h during major stress)

• Exogenous adrenal insufficiency: NO significant mineralocorticoid abnormalities
• No hyperpigmentation (ACTH not elevated)
• No fluid/electrolyte crisis (unlike primary Addison's)

9c. Cutaneous Adverse Effects

• Skin atrophy - thinning, increased fragility, spontaneous tearing
• Purpura/ecchymoses - especially dorsal forearms in patients >50 years (aggravates actinic purpura)
• Striae - especially abdomen, buttocks, thighs; permanent (unlike skin atrophy)
• Steroid acne - small, monomorphic follicular papules, forehead/cheeks/chest; manages like acne vulgaris
• Cushingoid habitus: buffalo hump, moon face, facial/neck fullness, supraclavicular/suprasternal fat, gynecomastia, protuberant abdomen, flattening of buttocks
• Hypertrichosis/hirsutism - fine vellus hairs on arms, back, beard area
• Hair loss - occurs in ~50% of patients on long-term high-dose CS
• Xerosis - generalized skin dryness
• Keratosis pilaris - may develop
• Impaired wound healing - decreased fibroblast proliferation

Source: Andrews' Diseases of the Skin, p.159; Wolverton Table 12-7

9d. Musculoskeletal Adverse Effects

• Bone loss begins in the first 6-12 months - rapid initial loss
• Trabecular bone > cortical bone affected (vertebrae, hip most at risk)
• Mechanism: decreased osteoblast function, increased osteoclast activity, decreased Ca²⁺ absorption, increased urinary Ca²⁺ excretion
• Fracture risk increases with cumulative dose

• All patients on CS >1 month: calcium 1000-1500 mg/day + vitamin D 400-800 IU/day
• Baseline DEXA scan; repeat every 1-2 years
• Bisphosphonates (alendronate, risedronate) - most patients on long-term CS warrant treatment
• Stop smoking, minimize alcohol
• Testosterone/estrogen for hypogonadism
• Teriparatide for established CS-induced osteoporosis

• Most common site: femoral head (bilateral in up to 50%)
• Also: humeral head, femoral condyles, talus
• Risk: doses >20-30 mg/day, cumulative dose >10 g
• Symptoms: groin/hip pain, worse with weight-bearing
• Early MRI most sensitive
• Treatment: core decompression (early), total hip arthroplasty (late)

• Proximal muscle weakness (pelvic girdle > shoulder girdle)
• Fluorinated CS (triamcinolone, dexamethasone) more likely to cause
• CK usually normal (type II fiber atrophy)
• Treatment: reduce dose, switch to non-fluorinated CS, physiotherapy

9e. Ophthalmologic Adverse Effects

• Slit-lamp exam at baseline and every 6-12 months on long-term therapy

9f. Metabolic Adverse Effects

• CS increase gluconeogenesis, peripheral insulin resistance, glycogen storage
• Most significant in pre-diabetic or diabetic patients
• Postprandial hyperglycemia predominantly
• Monitor fasting glucose; intensify diabetes management

• Increased triglycerides, LDL
• Decreased HDL
• Pancreatitis risk with triglycerides >800 mg/dL (Wolverton)

• Lipolysis + fat redistribution: central obesity, buffalo hump, moon face, supraclavicular fat
• Peripheral fat loss (limbs, buttocks)

9g. Cardiovascular Adverse Effects

• Hypertension - sodium and fluid retention (mineralocorticoid effect), increased cardiac output
• Methylprednisolone has less mineralocorticoid effect than prednisone → preferred in patients with hypertension
• Dyslipidemia contributes to atherosclerosis
• Increased cardiovascular event risk with long-term use

9h. Gastrointestinal Adverse Effects

• Peptic ulcer disease (PUD) - risk increases significantly with concurrent NSAIDs
• GI hemorrhage - risk highest with concurrent NSAIDs
• Bowel perforation - catastrophic; can be "silent" due to CS masking symptoms
• Pancreatitis - mainly from triglyceride elevation >800 mg/dL

9i. Infectious Complications

• Cellulitis, wound infections
• Impaired neutrophil function and migration
• Risk of masked signs (anti-inflammatory effect hides symptoms)

• Candidiasis (oral, esophageal, unusual locations)
• Aspergillosis, cryptococcosis (rare, more in multidrug regimens)

• Herpes zoster reactivation - increased risk
• CMV, widespread HSV
• Progressive Molluscum contagiosum

• Pneumocystis jirovecii (PCP) - primarily with multidrug regimens
• Strongyloides hyperinfection (screen in endemic area patients before starting CS!)

Source: Wolverton Table 12-10 (fatal complications); Andrews' Diseases of the Skin p.159

9j. Neuropsychiatric Effects

• Insomnia (early and common)
• Mood elevation/euphoria (initially)
• Irritability, emotional lability
• Depression (especially during taper)
• Psychosis (rare; high doses; more with history of psychiatric illness)
• Cognitive impairment with long-term use

9k. Potentially Fatal Complications (Wolverton Table 12-10)

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10. MONITORING GUIDELINES (Wolverton Box 12-6)

Baseline Assessment

• Blood pressure, weight
• Height/weight on growth chart (children)
• Ophthalmoscopy for cataracts

• TB screening (tuberculin skin test OR IFN-γ releasing assay + CXR)
• Fasting glucose and triglycerides
• Potassium level
• Bone mineral density (DEXA) if anticipating >3 months

Follow-Up (Long-term pharmacologic dose)

• Blood pressure, weight
• Growth chart (children)
• Thorough history for adverse effects

• Ophthalmologic examination (cataracts, glaucoma, IOP)

• Potassium level
• Fasting glucose
• Fasting triglycerides

• AM cortisol level (or other test of HPA axis function)

• Cardiac monitoring
• Daily electrolytes and glucose

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11. DRUG INTERACTIONS (Wolverton Table 12-14)

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12. SPECIAL POPULATIONS

12a. Pregnancy

• Prednisone/prednisolone: preferred (poor placental transfer; minimally metabolized to active form by placenta)
• Avoid dexamethasone and betamethasone for maternal indications (cross placenta readily)
• Risk: cleft palate (first trimester, high doses), IUGR, neonatal adrenal suppression
• Category C (old classification); risk/benefit discussion essential
• Monitor neonates born to mothers on CS for adrenal suppression

12b. Children

• Growth suppression: use lowest possible dose; alternate-day therapy preferred
• HPA suppression: more significant per kg compared to adults
• Prefer prednisolone (better oral bioavailability in children)
• Pediatric dermatology indications: erythrodermic atopic dermatitis, pustular psoriasis, childhood pemphigus, systemic JDM, pyoderma gangrenosum, SLE

12c. Elderly

• Higher risk of: osteoporosis, DM, HTN, cataracts, infections
• Bisphosphonate prophylaxis more urgently needed
• More likely to have concurrent NSAIDs → higher GI risk

12d. Liver Disease

• Use prednisolone NOT prednisone (prednisone cannot be converted to active form)
• Higher free fraction due to low albumin = greater biological effect at given dose → consider lower dose

12e. Androgen-Excess Disorders (Adrenal Origin)

• Timing differs: use late evening/nocturnal dosing (suppress ACTH at its overnight surge)
• Drug choice: dexamethasone (0.25-0.5 mg at bedtime) preferred
• Goal: suppress adrenal androgen production while maintaining HPA regulation
• Contrast to standard anti-inflammatory use (morning dosing)

Source: Wolverton Chapter 12, Q12-5

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13. STEROID TAPERING AND WITHDRAWAL

Principles of Tapering

1. Taper rate should match disease activity and duration of therapy
2. Rapid taper risk: disease rebound (especially pemphigus, vasculitis)
3. Slow taper risk: prolonged side effects, prolonged HPA suppression

Suggested Taper Strategies

• Reduce by 10-20% of current dose every 1-2 weeks
• Switch to alternate-day once daily dose reaches <30 mg/day

• Reduce by 10% of current dose per week (for doses >20 mg)
• Reduce by 1-2.5 mg/month when approaching physiologic range (5-10 mg/day)
• Consider AM cortisol testing before complete cessation

• Never reduce dose during active infection or disease flare
• Patient education: do NOT stop abruptly
• Provide steroid alert card for all patients on long-term CS

Steroid Alert Card - Key Message

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14. PULSE IV CORTICOSTEROID THERAPY

Protocol

• Drug: Methylprednisolone (preferred)
• Dose: 500-1000 mg/day (or 15 mg/kg/day, max 1000 mg)
• Duration: 3-5 consecutive days
• Route: IV infusion over 1-2 hours

Dermatologic Indications

• Pemphigus vulgaris (refractory or rapidly progressing)
• Bullous pemphigoid
• Sweet's syndrome
• Urticarial vasculitis
• Refractory alopecia areata
• SJS/TEN (early, severe)
• Dermatomyositis

Advantages Over Oral

• Quicker initial remission
• Lower cumulative dose compared to equivalent oral
• Comparable efficacy to 1-2 mg/kg/day oral prednisone for pemphigus (meta-analysis of 6 studies)

Risks

• Sudden cardiac death (arrhythmia from acute K⁺/Mg²⁺ shifts)
• Atrial fibrillation
• Anaphylaxis
• Electrolyte disturbances
• Hyperglycemia
• Increased infection risk

Source: Wolverton pp.155-156

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15. STEROID-SPARING STRATEGIES

Why Steroid-Sparing?

• Reduce CS dose to minimize adverse effects while maintaining disease control
• Any topical or systemic adjunctive therapy that allows CS dose reduction qualifies

Common Steroid-Sparing Agents in Dermatology

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16. KEY TABLES AND FIGURES

Figure 1 - CS Structure-Function Relationships

BASIC STEROID NUCLEUS (Cyclopentanoperhydrophenanthrene ring)

         18
         CH₃
    12       17
   11   13   16
  1  9    14  15
 2   8  D  
  3  7  ring
   4  6
    5
    ↑
    Double bond 4,5 position
    + Ketone at C-3 → ESSENTIAL for activity

Key modifications that affect potency:
• 11-OH (cortisol) vs 11=O (cortisone) → 11β-OH is ACTIVE
• 9α-Fluoro → increases potency ~10x
• 16α/β-methyl → reduces mineralocorticoid activity
• 1,2-double bond (prednisone) → increases glucocorticoid potency

Figure 2 - NFκB Mechanism (adapted from Wolverton Figure 12-2)

ACTIVATION SIGNALS (IL-1β, TNF-α, LPS, etc.)
        ↓
IκB kinase activation
        ↓
IκB phosphorylation → degradation
        ↓
NFκB released (active) → nucleus
        ↓
Transcription of: cytokines, adhesion molecules, COX-2, PLA₂

CORTICOSTEROID INTERVENTION:
1. CS-GCR complex → ↑IκB synthesis → binds NFκB → inactivates
2. CS-GCR complex → directly binds free NFκB → blocks DNA binding
Result: Dramatic ↓ in inflammatory gene transcription

Figure 3 - Cushingoid Habitus

• Moon face (temporal wasting, round cheeks)
• Buffalo hump (dorsocervical fat pad)
• Supraclavicular fat pads
• Central obesity (truncal fat with purple striae)
• Thin extremities (muscle wasting)
• Easy bruising (dermal atrophy)
• Acne (steroid acne - monomorphic follicular papules)

Dose Equivalence Quick Reference Card

REMEMBER: These are EQUIVALENT doses - same anti-inflammatory effect:

Hydrocortisone    20 mg
Cortisone         25 mg     ← less potent
Prednisolone       5 mg     ← standard reference
Prednisone         5 mg
Methylprednisolone 4 mg     ← less mineralocorticoid
Triamcinolone      4 mg     ← no mineralocorticoid; depot IM
Dexamethasone    0.75 mg    ← most potent glucocorticoid
Betamethasone    0.6 mg     ← most potent; crosses placenta!

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17. VIVA VOCE QUESTIONS AND ANSWERS

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1. The CS-glucocorticoid receptor (GCR) complex induces increased synthesis of IκB → IκB binds and inactivates NFκB
2. The CS-GCR complex can directly bind to free NFκB → physically blocks its transcription factor activity

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1. Osteoporosis: DEXA scan at baseline and repeat annually; calcium 1000-1500 mg/day + vitamin D 800 IU/day from day 1; bisphosphonate (alendronate 70 mg weekly) for patients on >7.5 mg/day prednisone for >3 months; check estrogen status (postmenopausal → higher risk)
2. PUD/GI: PPI (omeprazole 20 mg/day) if on concurrent NSAIDs or aspirin; avoid NSAIDs if possible
3. Hyperglycemia/DM: Fasting glucose at baseline and every 3-4 months; alert patient about postprandial glucose elevation; refer to endocrinology if pre-diabetic
4. Infection: TB screening (TST/IGRA + CXR) before starting; Strongyloides serology if from endemic area; advise live vaccine avoidance; complete pneumococcal + influenza vaccination
5. Ophthalmologic: Baseline slit-lamp + IOP; repeat every 6-12 months
6. HPA axis: Aim to add steroid-sparing agent (azathioprine or rituximab) to allow CS dose reduction; provide steroid alert card
7. HTN: Monitor BP at each visit; methylprednisolone preferred over prednisone if HTN is a concern (less mineralocorticoid effect)
8. Metabolic: Fasting lipids; dietary advice; restrict carbohydrate/calorie intake (Wolverton Box 12-6, 12-7; Andrews' Diseases of the Skin p.159)

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• Gluconeogenesis at expense of protein (muscle, skin, bone) → muscle wasting, skin thinning, osteoporosis
• Lipolysis + fat redistribution → central fat accumulation (moon face, buffalo hump, supraclavicular fat, truncal obesity) with peripheral wasting
• Insulin resistance → hyperglycemia, acanthosis nigricans (occasional)
• Mineralocorticoid effect (mainly hydrocortisone) → sodium and water retention, hypokalemia

• Moon face, buffalo hump
• Plethora (facial)
• Skin thinning and fragility, easy bruising
• Purple striae (distinguish from white striae of simple obesity)
• Steroid acne (monomorphic)
• Hypertrichosis/hirsutism
• Impaired wound healing
• Hyperpigmentation (only in Addison's/primary adrenal failure - from elevated ACTH) (Wolverton pp.146-147; Andrews' Diseases of the Skin p.159)

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• Active peptic ulcer disease → add PPI, consider H. pylori eradication
• Uncontrolled diabetes → optimize glycemic control first; intensify monitoring
• Uncontrolled hypertension → optimize antihypertensive therapy; use methylprednisolone (less mineralocorticoid)
• Severe osteoporosis → preemptive bisphosphonate + Ca/VitD; minimize dose/duration
• Active systemic infection → treat infection first; CS may be needed for septic shock in selected cases
• Psychiatric history (esp. psychosis) → use minimum effective dose; psychiatric support
• Live virus vaccine recently given → delay CS if possible
• Active TB → treat TB first with appropriate antituberculous therapy
• Strongyloides (endemic area) → screen and treat before starting CS (risk of hyperinfection syndrome)

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• CRF can also be released from cerebral cortex and limbic system (via acetylcholine and serotonin)
• Alternative ACTH inducers: catecholamines, vasopressin
• These maintain some glucose homeostasis during stress
• Important: ACTH plays NO role in aldosterone (mineralocorticoid) production

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18. QUIZ WITH ANSWERS

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SUMMARY: SAFETY PRINCIPLES (Wolverton Box 12-7)

1. Prescribe CS only for appropriate, well-documented indications
2. Understand and use all possible measures to avoid the most serious complications
3. Thorough patient education reinforced by a handout; form a therapeutic partnership
4. Match the aggression of CS therapy with risk of the disease being treated
5. Find the lowest possible effective dose as soon as possible
6. Use a non-perfectionistic mindset for completeness of disease control
7. "Attack, then reasonably quickly retreat" (taper)
8. Seek physiologic or alternate-day doses within 1-2 months; if not possible → add steroid-sparing therapy
9. Proactively deal with precipitators of the underlying disease
10. In presence of relative contraindication → manage it medically to allow careful CS therapy
11. Anticipate → Prevent → Diagnose early → Manage adverse effects

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SOURCES

• Wolverton SE. Comprehensive Dermatologic Drug Therapy, 3rd Edition. Chapter 12: Systemic Corticosteroids (Primary source - all tables and boxes referenced from here)
• Andrews' Diseases of the Skin - Clinical Dermatology (Elsevier, 9780323547536). Chapter 6: Dermatology Therapeutics - Systemic Corticosteroids, pp.159-160
• Fitzpatrick's Dermatology (9780071837781). Block 6 (pp.610-611): Systemic CS in Sarcoidosis; Block 14 (pp.1550-1551): Systemic CS in Alopecia Areata
• Dermatology 2-Volume Set 5th Edition (Bolognial/Schaffer, 9780702082252). Chapter 103: Systemic CS in Infantile Hemangiomas
• A practical guide to the monitoring and management of the complications of systemic corticosteroid therapy. [PMC3765115] - Saag KG, Furst DE. Allergy Asthma Clin Immunol 2013
• Chu AWL et al. Systemic treatments for atopic dermatitis: Systematic review and network meta-analysis. J Allergy Clin Immunol 2023 [PMID: 37678577]
• Mateos-Haro M et al. Treatments for alopecia areata: network meta-analysis. Cochrane Database Syst Rev 2023 [PMID: 37870096]
• DermNet NZ - Systemic steroids: dermnetnz.org/topics/systemic-steroids
• IADVL User's Manual of Systemic and Topical Steroids

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Resident's Quick Recall Mnemonics:

"Pretty Patients Must Try Dex Because it's Long" = Prednisone/Prednisolone (Intermediate), Methylprednisolone (Intermediate), Triamcinolone (Intermediate), Dexamethasone + Betamethasone (Long-acting)

"FOMITE" for CS side effects: Fluid retention, Osteoporosis, Metabolic (DM/dyslipidemia), Infections, Thin skin (atrophy/striae), Eye (cataracts/glaucoma)

"Never Stop Suddenly" = All patients on >3 weeks pharmacologic CS must be tapered; provide steroid card