What is the pathophysiology, signs, symptoms, diagnosis, and management of drug-induced acne in young adults with a history of acne taking medications such as corticosteroids, testosterone, and antidepressants?

Drug-Induced Acne: Pathophysiology, Clinical Features, Diagnosis, and Management

Pathophysiology

Drug-induced acne results from medications disrupting normal pilosebaceous unit function through multiple mechanisms including increased sebum production (corticosteroids, testosterone), altered keratinization, and direct follicular inflammation. 1, 2

• Corticosteroids increase sebum production and alter sebaceous gland differentiation through glucocorticoid receptor activation, while also promoting follicular hyperkeratinization 3, 4
• Testosterone and anabolic steroids directly stimulate sebaceous gland growth and sebum production through androgen receptor binding 2, 4
• Antidepressants (particularly lithium) may trigger acne through unclear mechanisms, possibly involving altered sebaceous gland function and inflammatory pathways 2, 4
• The eruption typically lacks the comedonal component of acne vulgaris, presenting instead as a monomorphic inflammatory response 5, 1

Clinical Features and Diagnosis

Drug-induced acne presents as a sudden-onset, monomorphic eruption of inflammatory papules and pustules in unusual locations beyond typical seborrheic zones, occurring at atypical ages, with temporal relationship to drug initiation. 1, 2

Diagnostic Criteria

• Monomorphic pattern: Lesions appear uniform in size and stage, lacking the pleomorphic mix of comedones, papules, and cysts seen in acne vulgaris 5, 1
• Unusual distribution: Lesions extend beyond face and upper back to involve scalp, upper thorax, shoulders, and upper arms 1, 2
• Temporal relationship: Eruption begins days to weeks after drug initiation (corticosteroids typically within 2-4 weeks, testosterone within weeks to months) 2
• Atypical age: Onset in patients outside typical acne age range (prepubertal children or adults >30 years) 1, 2
• Resistance to conventional therapy: Poor response to standard topical acne treatments 1

Key Distinguishing Features by Drug Class

• Corticosteroid-induced: Facial rounding, weight gain, striae, and other cushingoid features accompany the acneiform eruption 3
• Testosterone-induced: Associated with virilization signs in females (hirsutism, voice deepening, clitoromegaly) 4
• Antidepressant-induced: May present with other medication side effects (tremor with lithium, sedation with other agents) 4

Management Algorithm

Step 1: Assess Severity and Drug Necessity

Determine whether the causative medication can be discontinued, dose-reduced, or must be continued at current dosing. 5, 1

• For non-essential medications or those with alternatives: discontinue the offending drug, which should result in lesion improvement within 2-4 weeks 2
• For essential medications (e.g., corticosteroids for autoimmune disease, testosterone for hypogonadism): proceed with acne-directed therapy while continuing the drug 5, 6

Step 2: Mild to Moderate Drug-Induced Acne (Essential Drug Must Continue)

Initiate combination topical therapy with benzoyl peroxide 2.5-5% plus topical retinoid (tretinoin 0.025-0.05% or adapalene 0.1-0.3%) applied nightly. 3, 5

• Add topical clindamycin 1% combined with benzoyl peroxide for additional inflammatory control 7
• Never use topical antibiotics as monotherapy due to rapid resistance development 7, 8
• Expect 6-8 weeks for initial improvement with topical therapy alone 3

Step 3: Moderate to Severe Drug-Induced Acne

Add oral doxycycline 100 mg daily combined with topical benzoyl peroxide and retinoid for widespread inflammatory lesions. 7, 8

• Limit oral antibiotic duration to 3-4 months maximum to prevent bacterial resistance 7, 8
• Alternative dosing: doxycycline 40 mg extended-release daily for anti-inflammatory effects with reduced GI side effects 7
• Avoid oral antibiotics as monotherapy—always combine with benzoyl peroxide 7, 8
• Take with food and remain upright for 30 minutes to minimize esophageal irritation 7

Step 4: Severe Nodular or Refractory Drug-Induced Acne

For severe nodular eruptions or cases failing conventional therapy, initiate oral isotretinoin 0.5-1 mg/kg/day while continuing the causative medication. 3, 6

• Isotretinoin successfully treats severe drug-induced acne without requiring discontinuation of the offending medication 6
• Start at 0.5 mg/kg/day for first month, then increase to 1 mg/kg/day as tolerated 3
• For corticosteroid-induced acne fulminans: start prednisone 0.5-1 mg/kg/day first, then slowly taper while introducing isotretinoin to prevent flare 3
• Mandatory iPLEDGE enrollment and monthly pregnancy testing for females of childbearing potential 3
• Monitor liver function tests and lipid panel at baseline and during treatment 3

Step 5: Adjunctive Therapy for Individual Nodules

For isolated large, painful nodules, inject intralesional triamcinolone acetonide 3.3-5 mg/mL (0.05-0.1 mL per lesion) for rapid flattening within 48-72 hours. 3, 9

• Use lowest effective concentration (dilute 10 mg/mL stock to 3.3-5 mg/mL with normal saline) to minimize atrophy risk 3, 9
• Not appropriate for multiple lesions—reserve for occasional stubborn cysts 3, 9
• Contraindicated at sites of active infection 3, 9

Critical Management Pitfalls

• Never discontinue essential medications prematurely: Drug-induced acne is manageable with appropriate dermatologic therapy without compromising treatment of the underlying condition 5, 6
• Avoid long-term oral corticosteroids for acne treatment: While low-dose prednisone (5-15 mg daily) shows efficacy, long-term adverse effects prohibit use as primary acne therapy 3
• Do not use topical or oral antibiotics beyond 3-4 months: Extended duration dramatically increases antibiotic resistance without additional benefit 7, 8
• Always transition to maintenance therapy: After completing oral antibiotics, continue topical retinoid indefinitely to prevent recurrence 7, 8

Special Considerations by Drug Class

Corticosteroid-Induced Acne

• Cosmetic changes including acne occur in 80% of patients after 2 years of corticosteroid treatment 3
• Cannot use systemic corticosteroids to treat corticosteroid-induced acne—this paradoxically worsens the condition long-term 3
• Consider dose reduction or transition to steroid-sparing agents when medically appropriate 3

Testosterone-Induced Acne in Females

• Consider adding spironolactone 50-100 mg daily, which blocks androgen receptors and reduces testosterone production 3
• Spironolactone achieves 75% IGA success when combined with benzoyl peroxide at 12 weeks 3
• Requires concurrent contraception due to feminization risk to male fetuses 3
• No routine potassium monitoring needed in healthy young women without risk factors 3

Antidepressant-Induced Acne

• Do not discontinue psychiatric medications without consulting prescribing psychiatrist—abrupt cessation risks psychiatric decompensation 5
• Standard acne therapy is effective while continuing the antidepressant 6
• Isotretinoin can be used safely with careful monitoring for depressive symptoms, though causality remains unproven 3