What is the cause of recurrent chills/rigors in a patient with Rheumatoid Arthritis (RA), secondary osteoporosis, and controlled hypothyroidism, with normal urine routine and culture?

Recurrent Chills/Rigors in Rheumatoid Arthritis with Normal Urine Studies

The most likely cause of recurrent brief chills/rigors in this patient is active rheumatoid arthritis disease activity itself, potentially with systemic extra-articular manifestations, though infection (particularly occult sources beyond urinary), medication-related effects, and coexisting conditions must be systematically excluded.

Primary Differential Considerations

Active RA Disease Activity

• Systemic inflammatory activity from RA can manifest as constitutional symptoms including chills and rigors, even when joint symptoms may not be prominent 1
• RA can affect practically any organ system including hematologic manifestations that may present with systemic symptoms 1
• The presence of inflammation should be established through acute phase reactants (ESR, CRP) and clinical assessment to guide further management 2

Infection Risk Assessment

• Patients with RA are at increased risk of infections, largely due to treatment-related immunosuppression 1
• While urine culture is normal, other occult infection sources must be considered:
  • Respiratory tract infections (given RA patients have recurrent respiratory infections as a comorbidity) 3
  • Bloodstream infections or endocarditis 1
  • Intra-abdominal sources 1
• Blood cultures, chest imaging, and comprehensive infectious workup beyond urine studies are essential 1

Medication-Related Considerations

• Disease-modifying antirheumatic drugs (DMARDs) and biologics used in RA treatment can cause various systemic reactions 2
• Some biologic agents may trigger infusion reactions or immune-related adverse events that could manifest as chills 2

Diagnostic Approach Algorithm

Step 1: Confirm Inflammatory Activity

• Measure ESR and CRP to assess for active systemic inflammation 2
• Assess disease activity using validated composite measures 4
• If inflammatory markers are elevated, this supports active RA disease activity as the cause 2

Step 2: Rule Out Infection

• Obtain blood cultures (at least 2 sets) during an episode of chills 1
• Complete blood count with differential to assess for leukocytosis or left shift 1
• Chest X-ray to exclude pulmonary infection 1
• Consider echocardiography if there are any cardiac murmurs or risk factors for endocarditis 1

Step 3: Assess for Extra-Articular Manifestations

• RA can present with systemic involvement including hematologic abnormalities that may cause constitutional symptoms 1
• Screen for rheumatoid vasculitis, though this is becoming rarer with better disease control 1
• Evaluate for other organ system involvement (cardiac, pulmonary, hematologic) 4, 1

Step 4: Consider Coexisting Conditions

• The possibility of misdiagnosis or coexistent mimicking disease should be considered, particularly in difficult-to-control RA 2, 5
• Evaluate for:
  • Crystal arthropathies 2
  • Still's disease (which characteristically presents with high spiking fevers and chills) 2
  • Systemic lupus erythematosus 2
  • Vasculitis 2

Management Implications

If Active RA Disease Activity is Confirmed

• Measure disease activity regularly and adjust therapy accordingly to achieve remission 4
• Consider escalation of DMARD therapy if disease activity remains high 5
• The primary treatment goal should be achieving clinical remission/inactive disease 4

If Infection is Identified

• Appropriate antimicrobial therapy based on culture results 1
• Consider temporary modification of immunosuppressive therapy in consultation with rheumatology 1

If No Clear Cause is Found

• Ultrasonography may be considered to confirm the presence of inflammatory activity when there is doubt based on clinical assessment 5, 6
• Reassess disease activity after 3-6 months and monitor for development of any new manifestations 5

Critical Pitfalls to Avoid

• Do not assume symptoms are solely from RA without excluding infection, as RA patients have significantly increased infection risk 1
• Do not escalate DMARD therapy based solely on symptoms without confirming inflammatory activity through objective measures 2, 6
• Recognize that brief (1-minute) episodes of chills/rigors are somewhat atypical for typical bacterial infections, which usually cause more sustained fever patterns 1
• Consider that the controlled hypothyroidism is unlikely to be the cause if thyroid function tests are truly normal 6
• Secondary osteoporosis itself does not cause chills/rigors, though it indicates chronic systemic inflammation from RA 7