What is the cause and treatment of severe chills without fever or pain in a patient with Takayasu arteritis?

Severe Chills in Takayasu Arteritis: Cause and Treatment

The severe daily chills without fever in your Takayasu arteritis patient most likely represent constitutional symptoms from active systemic inflammation, and should be treated immediately with high-dose oral prednisone (40-60 mg daily) combined with a steroid-sparing immunosuppressive agent such as methotrexate (20-25 mg/week). 1

Understanding the Clinical Presentation

Constitutional Symptoms as Disease Activity Markers

• Takayasu arteritis characteristically presents in two phases: an acute phase with constitutional symptoms (including chills, fatigue, malaise) and a chronic phase with vascular manifestations 1
• Constitutional symptoms occur in only 33% of patients at presentation, making them significant when present 2
• These systemic symptoms reflect active inflammatory disease even when fever is absent 1, 2
• The absence of fever does not exclude active inflammation—many patients with active Takayasu arteritis present without fever 2

Why Inflammatory Markers May Be Misleading

• A critical pitfall: ESR and CRP are elevated in only 50% of active cases and should not be relied upon solely for disease activity assessment 1
• Normal inflammatory markers do not exclude active disease requiring treatment 1
• Surgical bypass biopsies from clinically inactive patients showed histologically active disease in 44% of cases, demonstrating the disconnect between clinical appearance and true disease activity 2

Immediate Treatment Approach

First-Line Medical Management

• Initiate high-dose oral glucocorticoids (prednisone 1 mg/kg/day or 40-60 mg daily) immediately 1, 3
• Simultaneously add a non-glucocorticoid immunosuppressive agent, preferably methotrexate (20-25 mg/week), to minimize glucocorticoid toxicity and improve long-term outcomes 1, 3
• Do not use glucocorticoid monotherapy except for mild disease—combination therapy from the start reduces glucocorticoid toxicity and improves remission rates 1

Alternative Steroid-Sparing Agents

• Azathioprine (2 mg/kg/day) can be used if methotrexate is contraindicated or not tolerated 1, 3
• Reserve IV pulse methylprednisolone (500-1,000 mg/day for 3-5 days) only for life- or organ-threatening manifestations such as vision loss, stroke, cardiac ischemia, or limb ischemia 1

Management of Refractory Cases

Second-Line Biologic Therapy

• For patients failing initial therapy with glucocorticoids and conventional immunosuppressants, TNF inhibitors are recommended as the next step 1
• Tocilizumab should be reserved for cases where TNF inhibitors are contraindicated, ineffective, or not tolerated 1
• Leflunomide represents another option for patients resistant to conventional therapies 4

Essential Monitoring Strategy

Clinical Assessment Protocol

• Perform vascular examination at each visit, specifically checking for new bruits or pulse deficits to detect new stenoses 1
• Obtain four-extremity blood pressures at every assessment to identify blood pressure discrepancies >10 mmHg between arms 1
• Measure inflammatory markers (ESR, CRP) alongside clinical assessment, but do not rely on them exclusively 1

Imaging Surveillance

• Schedule noninvasive imaging (MRI/CT angiography or FDG-PET) every 3-6 months during active disease 1
• Continue long-term clinical monitoring even in apparent remission, as vascular changes can occur when disease appears clinically quiescent 1
• New arterial stenosis or vessel wall thickening in new territories on imaging warrants intensification of immunosuppressive therapy, even if clinically asymptomatic 1

Critical Pitfalls to Avoid

• Do not dismiss constitutional symptoms like chills as insignificant—they often represent active systemic inflammation requiring treatment escalation 1, 2
• Do not wait for fever or elevated inflammatory markers before treating—active disease can exist without these findings 1, 2
• Do not use glucocorticoid monotherapy for more than initial management—early addition of steroid-sparing agents improves outcomes 1
• Do not discontinue monitoring during clinical remission—histologic disease activity can persist despite clinical quiescence 1, 2

Glucocorticoid Tapering Strategy

• For patients achieving remission on glucocorticoids for ≥6-12 months, taper off glucocorticoids completely rather than maintaining long-term low-dose therapy 1
• Continue non-glucocorticoid immunosuppressive agents during and after taper to prevent relapse 1
• Approximately half of patients who achieve remission will later relapse, necessitating vigilant monitoring 2