Atopic Dermatitis Pharmacotherapy

Atopic dermatitis pharmacotherapy aims to repair the barrier, control inflammation and itch, prevent flares and treat infection. Emollients and topical anti-inflammatory drugs treat most patients; systemic immunosuppressants and targeted agents are for moderate to severe disease. Disease is driven by a type 2 immune response (interleukin-4, interleukin-13, interleukin-31) with barrier defects.

Mechanism. Emollients restore water content and lipid; steroids and calcineurin inhibitors suppress inflammation; crisaborole inhibits phosphodiesterase 4. Dupilumab blocks the shared interleukin-4 and interleukin-13 receptor; tralokinumab and lebrikizumab block interleukin-13; upadacitinib, abrocitinib and baricitinib inhibit Janus kinases. Ciclosporin, azathioprine, mycophenolate and methotrexate suppress lymphocytes.

Pharmacokinetics. Ciclosporin is a CYP3A4 substrate. Azathioprine is metabolised by thiopurine methyltransferase; low activity raises toxicity. Antibody drugs are given subcutaneously with half-lives of about 3 to 4 weeks. Janus kinase inhibitors are oral and cleared by CYP enzymes and the kidney.

Regimens.

• Emollient: apply liberally at least twice daily and after bathing; use 250 to 500 g weekly in children and 500 g or more weekly in adults. Bath for short periods in lukewarm water with soap substitute.
• Flares: mild steroid on face, flexures and young children; moderate to potent steroid on the trunk and limbs; once daily, using potent steroids for no more than 2 weeks and stepping down to a milder steroid or tacrolimus as skin clears. Proactive maintenance: apply twice weekly to previously affected sites.
• Tacrolimus ointment 0.03 or 0.1 percent twice daily for flares, twice weekly for maintenance; pimecrolimus 1 percent for mild disease.
• Wet wraps: emollient or dilute steroid under damp bandages for 3 to 7 days in severe flares, with monitoring for infection and adrenal effects.
• Itch: sedating antihistamine at night for sleep loss only (for example hydroxyzine, chlorphenamine); non-sedating antihistamines do not control eczema itch.
• Ciclosporin: 3 to 5 mg/kg daily in two doses, then reduce to the lowest effective dose; limit to 1 year if possible.
• Methotrexate: 10 to 15 mg once weekly (up to 25 mg) with folic acid 5 mg weekly; azathioprine 1 to 3 mg/kg daily after thiopurine methyltransferase testing where possible; mycophenolate mofetil 1 to 3 g daily.
• Dupilumab: adults 600 mg once, then 300 mg every 2 weeks; children dosed by weight. Tralokinumab: 600 mg once, then 300 mg every 2 weeks. Lebrikizumab: 500 mg at weeks 0 and 2, then 250 mg every 2 weeks, then every 4 weeks.
• Upadacitinib 15 or 30 mg daily; abrocitinib 100 or 200 mg daily; baricitinib 2 or 4 mg daily.
• Infection: flucloxacillin or cefalexin for overt bacterial infection (honey crusting, weeping, pustules); do not give antibiotics for colonisation alone. Suspected eczema herpeticum (punched-out erosions, fever, rapid spread) needs same-day aciclovir and referral.

Selection. Escalate when optimal topical therapy fails or sleep and quality of life are badly affected. Dupilumab is preferred in children from 6 months, in those with asthma, and where infection or malignancy is a worry; Janus kinase inhibitors give the fastest itch relief but need cardiovascular and thrombosis assessment. Ciclosporin is a short bridge to a long-term drug.

Class risks.

• Topical steroids: atrophy and adrenal suppression with misuse. Calcineurin inhibitors: burning and infection.
• Dupilumab, tralokinumab, lebrikizumab: conjunctivitis and keratitis, injection site reactions, facial redness, new joint pain; dupilumab can unmask cutaneous T-cell lymphoma in rare cases.
• Janus kinase inhibitors: serious infection including herpes zoster, thrombosis, major cardiovascular events and cancer (higher risk over 65 years, smokers, and those with vascular risk), acne, raised lipids and creatine kinase, cytopenias.
• Ciclosporin: hypertension, nephrotoxicity, infection.
• Azathioprine: marrow suppression, hepatitis, cancer. Methotrexate: marrow suppression, hepatitis, teratogenicity.

Interactions. Ciclosporin with CYP3A4 inhibitors and inducers, nephrotoxic drugs and NSAIDs; azathioprine with allopurinol (reduce dose by about 75 percent); Janus kinase inhibitors with strong CYP inhibitors or inducers; avoid live vaccines on immunosuppressants.

Monitoring.

• Ciclosporin: blood pressure and creatinine every 2 weeks at first, then monthly.
• Azathioprine and methotrexate: full blood count and liver tests every 2 weeks for 6 weeks, then every 3 months.
• Janus kinase inhibitors: blood count, lipids and liver tests at baseline, 4 weeks and 12 weeks, then every 3 to 6 months.
• Review response at 12 to 16 weeks; ask about eye symptoms on antibody treatment.

Special groups.

• Pregnancy: emollients, topical steroids and tacrolimus; ciclosporin and azathioprine if systemic drug needed; avoid methotrexate, mycophenolate and Janus kinase inhibitors.
• Children: weight-based regimens and growth review on prolonged steroids.
• Region: eczema is increasingly common in urban East Africa; recurrent infection, scabies and contact allergy from herbal and cosmetic creams often drive flares and should be excluded; high hepatitis B and tuberculosis prevalence calls for screening before systemic immunosuppression; targeted agents are costly and rarely available.