What treatment or further workup is recommended for a middle-aged or older adult patient with a 7-year history of Rheumatoid Arthritis (RA) taking plaquenil (hydroxychloroquine) who has developed dark spots on their back as a potential side effect of the medication?

Hyperpigmentation from Hydroxychloroquine: Evaluation and Management

The dark spots are likely hydroxychloroquine-induced hyperpigmentation, which requires dermatology referral for confirmation and consideration of treatment options, while simultaneously evaluating whether the RA is well-controlled enough to potentially discontinue or reduce the hydroxychloroquine dose. 1

Immediate Assessment Required

Confirm the Diagnosis

• Dermatology consultation is essential to definitively diagnose hydroxychloroquine-induced hyperpigmentation versus other causes of pigmentation changes 1
• Document the distribution, color (typically blue-gray or brown), and pattern of the pigmented lesions
• The FDA label warns of dermatologic toxicity with prolonged hydroxychloroquine use, though hyperpigmentation is not explicitly listed among the most serious adverse effects 1

Evaluate Current RA Disease Activity

• Assess whether the patient still requires hydroxychloroquine by measuring disease activity using validated tools (tender/swollen joint counts, patient global assessment, inflammatory markers) 2
• If the patient has been in sustained remission or low disease activity for ≥1 year on hydroxychloroquine, consider tapering or discontinuing the medication 2
• The 2015 ACR guidelines support cautious reduction of DMARD therapy in patients with sustained long-term remission 2

Critical Screening for Serious Toxicity

Mandatory Ophthalmologic Evaluation

• Ensure the patient has had recent retinal screening (within the past year), as retinal toxicity is the most serious concern with 7 years of hydroxychloroquine use 1
• The FDA label specifies that after 5 years of therapy, annual examinations including best corrected visual acuity, visual field testing (central 10 degrees, or 24 degrees if Asian descent), and spectral domain optical coherence tomography are required 1
• Risk factors for retinal damage include daily doses >6.5 mg/kg actual body weight, duration >5 years (which this patient exceeds), and renal impairment 1

Assess for Other Hydroxychloroquine Toxicities

• Screen for cardiac complications: obtain ECG to evaluate for conduction abnormalities (bundle branch block, AV block) or QT prolongation, as cardiomyopathy can occur with chronic use 1
• Evaluate for proximal muscle weakness and depressed deep tendon reflexes (signs of myopathy/neuropathy) 1

Management Algorithm

If RA is Well-Controlled

1. Consider discontinuing or tapering hydroxychloroquine if the patient has achieved sustained remission, as the hyperpigmentation may slowly improve after drug cessation 2
2. The EULAR 2013 recommendations support cautious reduction of conventional synthetic DMARDs in cases of sustained long-term remission 2
3. Monitor disease activity closely (every 1-3 months initially) after any medication adjustment 2

If RA Requires Continued DMARD Therapy

1. Switch to an alternative DMARD such as methotrexate, sulfasalazine, or leflunomide if hydroxychloroquine must be discontinued 2
2. Methotrexate should be the preferred alternative DMARD for most RA patients per ACR guidelines 2
3. Combination therapy with methotrexate plus other conventional DMARDs has demonstrated superior efficacy compared to monotherapy 3, 4

Treatment of the Hyperpigmentation Itself

• Dermatology can offer specific treatments such as topical depigmenting agents, chemical peels, or laser therapy, though evidence for efficacy in drug-induced hyperpigmentation is limited
• Emphasize that improvement may be slow (months to years) even after drug discontinuation
• Sun protection is essential to prevent worsening of pigmentation

Critical Pitfalls to Avoid

• Do not continue hydroxychloroquine without recent ophthalmologic screening in a patient with 7 years of exposure, as irreversible retinal damage can occur and may progress even after drug cessation 1
• Do not assume the pigmentation is benign without dermatology evaluation, as other serious dermatologic conditions must be excluded
• Do not abruptly discontinue hydroxychloroquine without a plan for alternative RA management if the disease is not in sustained remission, as this may lead to disease flare 5
• Note that hydroxychloroquine is specifically not recommended for psoriatic arthritis due to potential disease exacerbation, though this is not relevant for RA patients 2