Can hydroxychloroquine (HCQ) for Sjögren's syndrome explain a patient's lack of fever for twenty years?

Hydroxychloroquine's Role in Fever Prevention in Sjögren's Syndrome

Hydroxychloroquine used for Sjögren's syndrome is unlikely to explain a patient's lack of fever for twenty years, as the medication is not primarily known for its antipyretic effects but rather for its immunomodulatory properties in autoimmune conditions.

Mechanism of Action and Effects on Fever

• Hydroxychloroquine (HCQ) is commonly used in autoimmune conditions such as Sjögren's syndrome, systemic lupus erythematosus, and rheumatoid arthritis for its immunomodulatory effects 1
• The medication works through inhibition of tumor necrosis factor-alpha and interleukin-6 (IL-6), which may indirectly affect inflammatory processes 2
• While HCQ has immunomodulatory and anti-inflammatory properties, there is no evidence in the literature specifically supporting its role as a long-term fever preventative agent 1

HCQ in Sjögren's Syndrome Treatment

• HCQ is one of the most frequently prescribed immunosuppressants for Sjögren's syndrome, though evidence regarding its efficacy for the main symptoms (dryness, pain, and fatigue) is limited 3
• The JOQUER randomized clinical trial showed that HCQ did not significantly improve the primary symptoms of Sjögren's syndrome compared to placebo during 24 weeks of treatment 3
• An earlier two-year double-blind crossover trial found no beneficial clinical effect of HCQ for symptoms and signs of primary Sjögren's syndrome, despite decreases in IgG and IgM levels 4

Laboratory and Immunological Effects

• HCQ treatment in Sjögren's syndrome patients has been shown to decrease immunoglobulin levels (IgG and IgM) and may slightly reduce erythrocyte sedimentation rate (ESR) 4
• The medication plays an immunomodulatory role by regulating interferon proteins, chemokines, and BAFF levels, as well as potentially modifying gut microbiota 5
• These immunomodulatory effects could theoretically dampen some inflammatory responses, but complete prevention of fever for decades is not an established effect 1

Clinical Considerations

• Approximately 25-50% of patients with primary Sjögren's disease take HCQ, with common indications being arthritis, parotid gland enlargement, and sicca-only symptoms 5
• One small study showed that HCQ treatment for 30 weeks positively impacted unstimulated salivary flow rates in Sjögren's patients, but did not significantly change other objective or subjective complaints 6
• Long-term HCQ use requires monitoring for potential side effects, particularly retinal toxicity, with baseline ophthalmic examination and follow-up every 6 months 1

Alternative Explanations

• The absence of fever for twenty years is unlikely to be solely attributed to HCQ use and may be related to other factors:
  • Individual variation in immune response
  • Potential subclinical infections that didn't trigger significant fever response
  • Other medications the patient might be taking concurrently
  • Possible alterations in thermoregulatory mechanisms unrelated to medication

Important Caveats

• HCQ is primarily used in combination with doxycycline for treating chronic infections like Q fever, not specifically for fever management 2, 1
• The evidence supporting HCQ use in chronic infections is primarily from retrospective cohorts and in vitro studies 1
• There is insufficient evidence to recommend HCQ solely as an antipyretic agent in the absence of specific indications like autoimmune conditions 1