What is the role of antimalarials, such as hydroxychloroquine (HCQ), in treating dermatological conditions?

Role of Antimalarials in Dermatology

Hydroxychloroquine (HCQ) is a cornerstone therapy in dermatology due to its immunomodulatory and anti-inflammatory properties, with established efficacy in lupus erythematosus, where it is a first-line treatment, and numerous other autoimmune and inflammatory skin conditions. 1, 2

Mechanism of Action in Dermatological Conditions

Hydroxychloroquine works through several mechanisms that make it effective for skin disorders:

• Immunomodulatory effects: Interferes with cytokine production and antigen processing/presentation 1
• Anti-inflammatory properties: Inhibits tumor necrosis factor-alpha and interleukin-6 3
• Lysosomal stabilization: Affects pH-dependent steps of cellular processes 4

Established Dermatological Indications

Lupus Erythematosus

• First-line therapy for all forms of lupus erythematosus:

  • Systemic lupus erythematosus (SLE)
  • Discoid lupus erythematosus (DLE)
  • Subacute cutaneous lupus erythematosus

• Benefits in lupus:

  • Reduces disease flares (HR 2.50; 95% CI: 1.08–5.58) 1
  • Decreases progressive organ damage 1
  • Increases long-term patient survival 1
  • Reduces infection risk 1

Other Dermatological Conditions

• Lichen planus 2
• Polymorphic light eruption 2
• Porphyria cutanea tarda 2
• Granuloma annulare 2
• Cutaneous sarcoidosis 2
• Hair disorders:
  • Lichen planopilaris (LPP)
  • Frontal fibrosing alopecia (FFA)
  • Alopecia areata (variable efficacy) 5

Dosing Guidelines

• Weight-based dosing: ≤5.0 mg/kg based on actual body weight (provides low risk of toxicity) 1
• Standard dosing: 200-400 mg daily (often given as a single dose or divided into two doses) 1
• Renal adjustment: Reduce dose by 25% in patients with eGFR <30 ml/min per 1.73 m² 1

Monitoring and Safety

Ophthalmologic Monitoring

• Baseline retinal examination before starting therapy
• Regular ophthalmologic examinations every 6-12 months during treatment 1
• Risk of retinal toxicity increases with:
  • Higher cumulative doses
  • Longer duration of treatment (0.5% after 6 years, 7.5% in long-term users, >20% after 20 years) 1

Laboratory Monitoring

• Baseline complete blood count (CBC) and comprehensive metabolic panel (CMP)
• Periodic monitoring of liver function, CBC, and renal function 1, 6
• Severe laboratory abnormalities are rare (12% in one study, with only 3% being persistent) 6

Major Adverse Effects

1. Retinal toxicity: Most serious long-term complication, can be irreversible 1
2. Cardiac effects: QT prolongation and potential arrhythmias 1
3. Dermatologic reactions:
   • Drug eruptions/rash (most common)
   • Cutaneous hyperpigmentation
   • Pruritus
   • Acute generalized exanthematous pustulosis
   • Stevens-Johnson syndrome/toxic epidermal necrolysis (rare)
   • Hair loss 7
4. Hematologic: Hemolytic anemia (especially in G6PD deficiency) 1
5. Neurologic: Peripheral neuropathy 1

Special Considerations

• Pregnancy: Generally considered safe during pregnancy 1
• Pediatric use: Has been used in pediatric patients with rheumatic diseases for years 1
• Psoriasis: May worsen psoriasis, use with caution 8
• Drug interactions: Weak inhibitor of CYP2D6 and P-gp efflux protein 1

Clinical Pearls

• Don't avoid hydroxychloroquine solely due to fear of retinopathy; proper monitoring minimizes risk 1
• Don't discontinue for borderline ophthalmologic findings; the goal is to safely maintain this valuable medication 1
• Patient education is crucial regarding:
  • Reporting visual changes
  • Monitoring for neuropsychiatric symptoms
  • Using sun protection 1

Treatment Algorithm for Dermatologic Conditions

1. For lupus erythematosus:

   • Start with 200-400 mg daily
   • Evaluate response at 3-6 months (full effect may take 3-6 months)
   • Continue indefinitely if effective

2. For other inflammatory/autoimmune conditions:

   • Start with 200-400 mg daily
   • Trial of 3-6 months to assess efficacy
   • Consider combination therapy with other agents for refractory cases

3. For hair disorders (LPP, FFA):

   • Consider as monotherapy or in combination with topical or intralesional steroids
   • Evaluate response over 3-6 months 5

Hydroxychloroquine remains an essential medication in dermatology with a favorable risk-benefit profile when properly monitored. Its broad immunomodulatory effects make it valuable across numerous dermatologic conditions, particularly those with autoimmune pathophysiology.