For which autoimmune diseases is Plaquenil (hydroxychloroquine) effective?

Autoimmune Diseases for Which Plaquenil (Hydroxychloroquine) is Effective

Hydroxychloroquine is most definitively effective for systemic lupus erythematosus (including lupus nephritis), rheumatoid arthritis, and antiphospholipid syndrome, with emerging evidence supporting its use in Sjögren's syndrome, dermatomyositis, and IgA nephropathy. 1, 2, 3

Primary Indications with Strong Evidence

Systemic Lupus Erythematosus (SLE)

• Hydroxychloroquine is recommended for all patients with SLE unless contraindicated, as it reduces disease activity, organ damage accrual, risk of infections and thrombosis, and improves survival rates 1, 2, 4
• The drug contributes to inducing lupus nephritis remission, reduces steroid requirements, and improves the cardiometabolic profile 2, 3
• The KDIGO 2024 guidelines specifically recommend hydroxychloroquine for all lupus nephritis patients as background therapy 1
• Standard dosing is 200-400 mg daily, with a maximum of 5 mg/kg/day based on actual body weight to minimize retinal toxicity 5

Rheumatoid Arthritis (RA)

• Hydroxychloroquine improves cardiovascular risk factors in RA patients, including reducing total cholesterol, LDL-C, and triglycerides while increasing HDL-C 1
• The drug has favorable effects on joint inflammation and may protect against statin-induced diabetes 1, 2
• It is classified as a conventional disease-modifying antirheumatic drug (DMARD) with immunomodulatory properties 6, 4

Antiphospholipid Syndrome

• Hydroxychloroquine is effective for both primary and secondary thrombosis prevention in antiphospholipid syndrome 2, 4
• The drug's antithrombotic properties make it particularly valuable in this condition 2

Secondary Indications with Moderate Evidence

Sjögren's Syndrome

• Hydroxychloroquine increases lacrimal quality and improves both objective and subjective inflammatory markers 2, 4
• The drug reduces T-cell and B-cell hyperactivity, which is relevant to Sjögren's pathophysiology 4

Dermatomyositis

• The Mayo Clinic recommends 200 mg twice daily (5 mg/kg) for dermatomyositis 5
• Hydroxychloroquine may improve dermatological manifestations in this condition 2

IgA Nephropathy

• Recent studies demonstrate reduction in proteinuria with hydroxychloroquine therapy 3
• Research is ongoing to establish its role as a therapeutic option in this glomerular disease 3

Emerging or Less-Established Indications

Other Conditions Under Investigation

• Sarcoidosis: May have positive effects on disease manifestations 2
• Still's Disease: Potential beneficial effects reported 2
• Primary Membranous Nephropathy: Currently under investigation 3
• Systemic Vasculitis and Anti-GBM Disease: Research underway 3

Mechanism of Action Across Autoimmune Diseases

Hydroxychloroquine functions as an immunomodulatory agent rather than a true immunosuppressant, with effects significantly weaker than conventional immunosuppressants like azathioprine or mycophenolate 6, 4. The drug works by:

• Interfering with lysosomal activity and antigen presentation 3
• Reducing inflammatory pathways and Toll-like receptor activation 2, 4
• Decreasing transcription of pro-inflammatory cytokines 3, 4
• Inhibiting autophagy 3

Critical Safety Considerations

Retinal Toxicity Monitoring

• Baseline ophthalmologic examination is mandatory before initiating therapy 5
• Annual screening should begin after 5 years for low-risk patients, or after 1 year for high-risk patients (eGFR <60 ml/min/1.73 m², dose >5 mg/kg/day, concomitant tamoxifen use) 1, 5
• Retinopathy risk is 0.5% after 6 years, increasing to 7.5% in long-term users and potentially >20% after 20 years of treatment 1
• The drug should not be discontinued prematurely based on questionable findings, as retinopathy develops slowly and suspicious findings should be rechecked after several months 1

Dosing Adjustments

• Maximum dose of 5 mg/kg/day based on actual body weight to minimize retinal toxicity 5
• In patients with eGFR <30 ml/min/1.73 m², reduce dose by 25% 1, 5
• Doses of 2-3 mg/kg/day may not achieve adequate blood levels and could be associated with higher flare rates 1
• Target blood hydroxychloroquine level above 0.6 mg/L may be associated with lower risk of lupus nephritis flare 1

Pre-Treatment Screening

• Check G6PD levels in men of African, Asian, or Middle Eastern origin before starting treatment due to hemolysis risk, though this risk appears low 1, 5
• Baseline ECG is recommended due to potential QT prolongation 5

Common Pitfalls to Avoid

• Do not assume hydroxychloroquine carries the same infection risk as true immunosuppressants like mycophenolate or calcineurin inhibitors, as this leads to unnecessary drug discontinuation during minor infections 6
• Do not stop the drug prematurely based on subtle or borderline ophthalmologic findings without repeat testing or retina consultation, especially in patients with active rheumatic disease 1
• Do not use doses below 5 mg/kg/day thinking it is safer, as inadequate dosing may lead to subtherapeutic blood levels and increased disease flare rates 1
• Hypersensitivity skin reactions can reduce compliance, but desensitization protocols are effective in overcoming these reactions in most patients 7