Systemic Therapy In Dermatology: Complete Clinical Guide
Comprehensive guide to systemic medications for inflammatory skin diseases like psoriasis, eczema, and urticaria.
This article provides an overview of systemic therapies used in dermatology for managing inflammatory skin diseases, including
psoriasis
,atopic dermatitis (eczema)
, andurticaria
. Systemic medications are oral or injectable drugs that treat widespread or severe conditions affecting more than 10-20% of the body surface area, pustular or erythrodermic forms, or cases with significant functional impairment.Introduction to Systemic Therapy in Dermatology
Systemic therapy is reserved for moderate-to-severe skin conditions unresponsive to topical treatments. These include autoimmune bullous diseases, lupus erythematosus, severe eczema, and recalcitrant psoriasis. Drugs work by suppressing inflammation, modulating immune responses, or inhibiting cell proliferation. Key agents target cytokines, T-cells, or metabolic pathways. Selection depends on disease severity, patient age, comorbidities, and risks like infections or organ toxicity. Regular monitoring of blood counts, liver, kidney function, and bone density is essential.
Therapies are categorized as corticosteroids, traditional immunosuppressants (e.g., methotrexate, ciclosporin), retinoids, and biologics. Short-term use minimizes side effects, while long-term requires prophylaxis.
Systemic Corticosteroids (Steroids)
**Systemic steroids**, derived from cortisol, exert profound anti-inflammatory effects and are used short-term for acute flares in eczema, autoimmune bullous diseases, and lupus. Prednisone (40-60 mg daily initially) controls symptoms in 2-4 weeks, then tapers to the lowest maintenance dose. Administer as a single morning dose to mimic natural cortisol rhythms and reduce hypothalamic-pituitary-adrenal (HPA) axis suppression.
Dosing Classification:
- Low dose: Prednisone <7.5 mg/day
- Medium dose: 7.5-30 mg/day
- High dose: 30-100 mg/day
- Pulse therapy: >100 mg/day short-term
Short-term (<1 month) is relatively safe; long-term (>3 months) risks include osteoporosis, hypertension, diabetes, infections, avascular necrosis, myopathy, glaucoma, mood changes, and psychosis. Avoid in psoriasis due to rebound flares.
Prophylaxis and Monitoring for Systemic Steroids
For >7.5 mg/day prednisone >3 months, assess bone mineral density (BMD) at spine/hip baseline. Stimulate bone resorption; supplement calcium/vitamin D, consider bisphosphonates. Calculate cardiovascular risk (Framingham score); monitor lipids at baseline, 1 month, then 6-12 months. Screen for tuberculosis before biologics or long-term use. Psychiatric effects like anxiety resolve with dose reduction.
| Risk | Prophylaxis/Monitoring |
|---|---|
| Osteoporosis | BMD scan, calcium 1200 mg/day, vitamin D 800 IU/day, bisphosphonates if high risk |
| Hypertension/Diabetes | BP/glucose checks every 3-6 months, lifestyle advice |
| Infections | Prophylactic antivirals if history, vaccinations |
| Avascular Necrosis | MRI if suspected hip pain; conservative Rx then surgery |
Methotrexate
**Methotrexate**, a folic acid analogue, is first-line for psoriasis and psoriatic arthritis (50-70% achieve PASI-75 in 5-6 months). Weekly dosing (2.5-25 mg oral or divided over 36 hours) suppresses cytokines (TNF-α, IL-10/12), reduces T-cell activation, and inhibits DNA synthesis at higher doses. Start low (2.5-5 mg) in elderly, low body weight, or renal impairment; escalate gradually.
Folic acid (1-5 mg daily) mitigates nausea and macrocytic anemia. Monitor full blood count (FBC), renal/liver function every 1-3 months initially, then 3-6 months. Effective for eczema off-label.
Methotrexate Adverse Effects and Monitoring
- Hepatotoxicity (fibrosis/cirrhosis risk)
- Bone marrow suppression (pancytopenia)
- Pneumonitis
- Teratogenicity (contraindicated in pregnancy)
Liver biopsy if cumulative dose >1.5g or abnormal enzymes.
Ciclosporin (Cyclosporine)
**Ciclosporin** (2.5-5 mg/kg/day) rapidly controls severe psoriasis; funded in New Zealand for this indication. Inhibits T-cell activation. Monitor renal function and blood pressure closely; dose reduce or interrupt if impaired. Short-term use (up to 1 year) due to nephrotoxicity, hypertension, hypertrichosis, gingival hyperplasia.
Acitretin and Other Retinoids
**Acitretin** (10-50 mg daily) for severe psoriasis, especially with phototherapy. Reduces keratinocyte proliferation. Requires Special Authority; monitor lipids, liver function, pregnancy testing (teratogenic). Avoid in women of childbearing potential unless using contraception.
Biologics and Targeted Therapies
Biologics target specific immune pathways for moderate-severe psoriasis.
- Infliximab: Anti-TNFα monoclonal antibody; IV loading then every 8 weeks. 80% PASI-75; combine with methotrexate.
- Etanercept: TNF inhibitor; subcutaneous, excellent safety for psoriatic arthritis/psoriasis.
- Alefacept: Binds CD2 on T-cells; 33% PASI-75.
Screen for TB; monitor infections. Less effective options include azathioprine, hydroxycarbamide.
Systemic Therapy for Atopic Dermatitis
For severe eczema, options include antihistamines (sedating for itch), short-course systemic steroids (avoid long-term), immunosuppressants (methotrexate, ciclosporin), biologics like dupilumab (anti-IL-4/13), and Janus kinase (JAK) inhibitors. Ciclosporin effective short-term; methotrexate shows promise off-label.
Systemic Therapy for Urticaria
Chronic urticaria responds to H1-antihistamines; refractory cases use omalizumab (anti-IgE biologic), ciclosporin, or methotrexate.
General Monitoring and Safety
All systemic therapies require baseline assessments (FBC, U&E, LFT, lipids, BP) and regular follow-up. Pregnancy testing for teratogens. Lifestyle: smoking cessation, diet, exercise reduce CVD risk.
Frequently Asked Questions (FAQs)
Q: When is systemic therapy indicated for psoriasis?
A: For >10-20% body surface area, pustular/erythrodermic types, psoriatic arthritis, or recalcitrant localized disease.
Q: Are systemic steroids safe long-term?
A: No; >3 months at >7.5 mg/day prednisone risks osteoporosis, infections; use prophylaxis and monitor.
Q: What is the starting dose for methotrexate in psoriasis?
A: 2.5-5 mg weekly, escalate to 25 mg; folic acid supplementation advised.
Q: Can biologics cure psoriasis?
A: No, they control symptoms; remissions possible but relapse on cessation.
Q: Is monitoring required for all systemic therapies?
A: Yes, blood tests, organ function, and infection screening are mandatory.
References
- Prophylaxis for systemic steroid treatment — DermNet NZ. 2023. https://dermnetnz.org/topics/prophylaxis-systemic-steroid
- Methotrexate Guidelines — DermNet NZ / Sussex CDS. 2019-10-01. https://sussexcds.co.uk/wp-content/uploads/2019/10/Methotrexate_NZDermNet.pdf
- Systemic therapy for psoriasis — DermNet NZ. 2023. https://dermnetnz.org/cme/scaly-rashes/systemic-therapy-for-psoriasis
- Systemic steroids — DermNet NZ. 2023. https://dermnetnz.org/topics/systemic-steroids
- Treatment of psoriasis — DermNet NZ. 2023. https://dermnetnz.org/topics/treatment-of-psoriasis
- Systemic therapy overview — DermNet NZ. 2018-07-01. https://dermnetnz.org/topics/systemic-therapy
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