Why would an adult patient with Sjogren's syndrome, small fiber peripheral neuropathy, allergic rhinitis, and mild anxiety, taking hydroxychloroquine (Plaquenil), fexofenadine (Allegra), gabapentin (Neurontin), and escitalopram (Lexapro) 5mg, not have a fever for 20 years?

Absence of Fever in a Patient with Sjögren's Syndrome

The absence of fever for 20 years in this patient with Sjögren's syndrome is most likely due to the immunomodulatory effects of hydroxychloroquine, which can suppress the inflammatory response that typically produces fever.

Hydroxychloroquine's Impact on Fever Response

• Hydroxychloroquine has significant immunomodulatory and anti-inflammatory properties that can regulate interferon proteins, chemokines, and BAFF levels, potentially suppressing the normal fever response 1
• It plays a central role in modulating lymphoproliferation in Sjögren's syndrome patients, which may prevent the inflammatory cascade that typically leads to fever 2
• The medication decreases immunoglobulins and ESR levels, both markers of inflammation that are often elevated during febrile episodes 1

Sjögren's Syndrome and Altered Immune Response

• Sjögren's syndrome is characterized by lymphocytic infiltration of exocrine glands, autoantibody production, and polyclonal hypergammaglobulinemia, creating a baseline inflammatory state 3
• Hydroxychloroquine has been shown to significantly decrease total immunoglobulin G (IgG) and IgA levels, which are components of the immune response involved in fever generation 2
• The medication reduces erythrocyte sedimentation rate (ESR), a marker of systemic inflammation that typically rises during febrile episodes 2

Medication Effects on Temperature Regulation

• Long-term use of hydroxychloroquine (as in this patient's case) can lead to sustained immunomodulation that may alter the normal febrile response to infections or inflammatory triggers 4
• Hydroxychloroquine modifies gut microbiota, which plays a role in immune system regulation and potentially temperature homeostasis 1
• The combination of medications this patient is taking (hydroxychloroquine, fexofenadine, gabapentin, and escitalopram) may have synergistic effects on temperature regulation pathways 5

Clinical Implications and Monitoring

• While the absence of fever may seem beneficial, it could potentially mask infections or disease flares that would normally present with elevated temperature 5
• Regular monitoring for other signs of infection or disease activity is crucial in patients who may not mount a typical febrile response 5
• Patients on hydroxychloroquine require baseline and periodic ophthalmologic examinations due to potential retinal toxicity, especially with long-term use 4

Other Potential Contributing Factors

• Small fiber peripheral neuropathy may affect autonomic nervous system function, potentially including temperature regulation 5
• Gabapentin, used for neuropathic pain, can affect central nervous system function and potentially influence temperature regulation 5
• Fexofenadine (antihistamine) may suppress some inflammatory pathways that contribute to fever generation 5

Clinical Recommendations

• Continue monitoring for non-temperature indicators of infection or disease flares, as this patient may not develop fever as a warning sign 5
• Consider periodic laboratory evaluations to detect subclinical inflammation or infection that would normally present with fever 5
• Educate the patient about recognizing other signs of infection or disease flares that don't involve temperature elevation 5
• Maintain current medication regimen if disease control is adequate, as hydroxychloroquine has an excellent benefit-risk profile for Sjögren's syndrome 1

While unusual, the absence of fever for an extended period in this patient with Sjögren's syndrome is most likely a consequence of the immunomodulatory effects of hydroxychloroquine, potentially enhanced by her other medications and underlying conditions.