Drug-Induced Acne

Drug induced acne is an acneiform eruption caused by medication, which presents with uniform inflammatory papules and pustules, often without comedones, on the face, chest and back. It can begin within days of starting the drug.

It occurs in people exposed to corticosteroids, androgens and anabolic steroids, lithium, isoniazid, phenytoin, phenobarbital, azathioprine, ciclosporin, sirolimus, halogens (bromides and iodides), vitamin B6 and B12 supplements, danazol and some progestogens. An epidermal growth factor receptor inhibitor rash affects up to 50 to 90% of people treated with cetuximab, erlotinib and related drugs.

Onset is typically 1 to 4 weeks after starting (EGFR inhibitors within 1 to 2 weeks), and the eruption usually clears within weeks to months of withdrawal. Severe rash can limit cancer treatment, so prompt treatment and dose adjustment matter.

Pathophysiology.

Mechanisms vary by drug. Corticosteroids and androgens stimulate sebaceous activity and follicular inflammation. EGFR and MEK inhibitors block epidermal growth factor signalling in follicular keratinocytes, which causes abnormal follicular keratinisation, follicular rupture and neutrophilic inflammation. Halogens are excreted in sebaceous glands and cause irritation.

• Sudden crops of uniform red papules and pustules on the face, scalp, chest and upper back, with few or no comedones.
• EGFR inhibitors: papulopustular rash in seborrhoeic areas, often with dry skin, itch, paronychia and fissures.
• Severity can range from mild to severe, with pain, impaired function and secondary infection.
• Resolution after stopping the drug, though EGFR inhibitor rash can leave dry skin and pigment change.

Red flags.

• Widespread pustules with fever or pain, suggesting infection or acute generalised exanthematous pustulosis.
• Severe EGFR inhibitor rash (many lesions with pain and limiting daily activity) or superinfection.
• Scarring nodules or sudden systemic upset.

• Clinical diagnosis from the timing relative to a drug and the monomorphic papulopustules.
• Review of all medicines, supplements and anabolic agents.
• Swab for bacteria, and for herpes simplex or fungus if the picture is atypical, and potassium hydroxide microscopy for Malassezia.
• Grading of EGFR inhibitor rash by extent, symptoms and impact.

Differential diagnosis. Acne vulgaris, folliculitis (bacterial or Malassezia), rosacea, perioral dermatitis, eosinophilic folliculitis, acute generalised exanthematous pustulosis and herpes simplex or zoster.

• Withdraw or substitute the causative drug when this is safe. Do not stop essential drugs such as antiepileptics or immunosuppressants without specialist advice.
• EGFR inhibitor prevention: doxycycline 100 mg twice daily (or minocycline 100 mg daily) for 6 to 8 weeks from the start of treatment, with emollients, sunscreen and hydrocortisone 1% cream once daily on the face.
• Established mild to moderate rash: topical clindamycin 1% twice daily (or erythromycin 2%), hydrocortisone 1% cream once daily, and oral doxycycline 100 mg twice daily for 6 to 8 weeks.
• Severe rash: increase to oral doxycycline 100 mg twice daily with a topical treatment, consider prednisolone 0.5 mg/kg/day for 5 to 7 days, hold or reduce the EGFR inhibitor dose with oncology agreement, and treat infection (flucloxacillin 500 mg four times daily for 7 days).
• Other drug induced acne: benzoyl peroxide 2.5 to 5% once daily, adapalene 0.1% at night, and oral doxycycline 100 mg daily for 8 to 12 weeks for moderate disease.
• Isotretinoin 0.5 mg/kg/day is used rarely for refractory non-cancer cases, with contraception, monthly pregnancy tests and lipid and liver monitoring.

Monitoring. Review at 2 weeks and 4 weeks in EGFR inhibitor treatment, with grading at each visit.

Referral and escalation. Refer to dermatology and oncology for severe rash that threatens cancer treatment.

Special groups. Avoid tetracyclines in pregnancy and in children under 12 years, and use erythromycin 500 mg twice daily or azelaic acid 15% gel twice daily.