What is the role of Hydroxychloroquine (HCQ) in the treatment of psoriasis?

Hydroxychloroquine (HCQ) in Psoriasis: Contraindication and Risk of Exacerbation

Hydroxychloroquine is contraindicated in patients with psoriasis as it can precipitate severe flares of psoriatic skin lesions and should be avoided in this population. 1

Mechanism and Evidence for Contraindication

• Hydroxychloroquine (HCQ) is specifically listed as contraindicated in psoriasis patients in the FDA drug label, which states: "Administration of hydroxychloroquine sulfate to patients with psoriasis may precipitate a severe flare-up of psoriasis. Avoid hydroxychloroquine sulfate in patients with psoriasis, unless the benefit to the patient outweighs the possible risk." 1

• Antimalarials such as chloroquine and hydroxychloroquine can severely worsen pre-existing psoriasis, as documented in multiple clinical guidelines and research studies 2, 3

• The exacerbation mechanism appears to involve:

  • Alteration of enzymes involved in epidermal proliferation 3
  • Inhibition of transglutaminase activity, causing breaks in epidermal barrier function 4
  • Stimulation of IL-6 overexpression in keratinocytes, which promotes inflammatory cascades 5

Clinical Evidence and Observations

• Studies estimate that up to 18% of patients with psoriasis will experience an exacerbation of their disease following antimalarial therapy 3

• Unlike some other psoriasis-triggering medications, antimalarials typically don't induce new-onset psoriasis but rather trigger flares in those with existing or latent disease 3

• Severe adverse reactions documented in case reports include:

  • Exfoliative erythroderma developing shortly after HCQ initiation for psoriatic arthritis 6
  • Marked exacerbation of psoriatic skin lesions in patients treated with HCQ 7

Guidelines and Recommendations

• Multiple treatment guidelines for psoriasis and psoriatic arthritis explicitly recommend against using hydroxychloroquine:
  • "Gold salts, chloroquine and hydroxychloroquine also are not recommended for use in PsA [Psoriatic Arthritis]." 8
  • This contraindication appears in both dermatology and rheumatology guidelines, emphasizing the cross-specialty consensus on avoiding these agents 8, 2

Alternative Treatment Options for Psoriasis

• First-line systemic treatments for psoriasis with stronger evidence of benefit include:
  • Methotrexate, cyclosporine, and acitretin (FDA-approved options) 8
  • Phototherapy options including narrowband UVB (NB-UVB) which has demonstrated superior efficacy to broadband UVB 8
  • Newer biologic agents and small molecules like apremilast 8

Special Considerations

• If a patient has both psoriasis and systemic lupus erythematosus (SLE), the risk of psoriasis exacerbation must be carefully weighed against the potential benefits for SLE management 8

• For patients with psoriatic arthritis without significant skin involvement, traditional DMARDs like methotrexate, sulfasalazine, or leflunomide should be considered instead of hydroxychloroquine 8

• Animal models confirm that HCQ can worsen psoriasis-like skin inflammation through multiple immunological mechanisms, including increased IL-6 expression and promotion of Th17 responses 5

In conclusion, hydroxychloroquine has no therapeutic role in psoriasis management and is contraindicated due to its well-documented risk of triggering severe psoriatic flares. Alternative treatment options with established efficacy and safety should be utilized instead.