Takayasu Arteritis

Definition and Overview

• Predominantly affects young women (female:male ratio up to 10:1)
• Onset typically before age 40 (most often in the 2nd-3rd decade)
• More common in Japan, Southeast Asia, India, and South America
• Often called "pulseless disease" or "aortic arch syndrome"

Pathogenesis

• Adventitial thickening with leukocyte accumulation in the media
• Infiltration by dendritic cells, T and B lymphocytes, macrophages, and multinucleated giant cells
• In TA specifically, the majority of lymphocytes are perforin-secreting killer cells (cytotoxic T cells and NK cells) - oligoclonal T cell receptors suggest a response to a specific but unknown antigen
• Growth factor-driven mesenchymal proliferation leads to intimal hyperplasia and fibrosis, causing stenosis or occlusion
• Local matrix metalloproteinase (MMP) synthesis may predispose to aneurysmal dilation
• Late phase: intimal proliferation, medial necrosis with scarring, adventitial fibrosis

Clinical Phases

• Fever, night sweats, arthralgia, malaise, profound fatigue, lethargy
• Weight loss

• Upper limb claudication
• Carotidynia (tenderness over carotids) in up to 25% of patients
• Absent or diminished radial and carotid pulses
• Bruits over stenotic vessels
• BP difference between arms ≥20 mmHg

• Subclavian and common carotid arteries (most frequent)
• Aorta (can be involved throughout its length)
• Pulmonary arteries (up to 50% of patients)
• Renal arteries (causes renovascular hypertension in 40-60%)

• 90% have stenotic/occlusive lesions

• ~25% have aneurysms
• Aortic valve regurgitation and coronary arteritis may occur

Imaging Findings

• Conventional arteriography - gold standard for luminal assessment
• CT angiography (CTA) - detects wall thickening and luminal changes
• MR angiography (MRA) - preferred for follow-up (no radiation); can detect mural inflammation
• 18F-FDG-PET-CT - best for detecting active inflammation
• Doppler ultrasound - useful for accessible vessels (carotid, subclavian)

Laboratory Findings

• Elevated ESR and CRP (markers of active inflammation)
• Mild anemia
• Elevated gamma-globulins
• Some patients: anti-endothelial cell antibodies, elevated pentraxin-3
• ANA, VDRL, complement levels are normal
• Hypertension in 40-60% (renal artery stenosis, decreased aortic elasticity)

Classification Criteria

ACR 1990 Criteria (≥3 of 6 = sensitivity 91%, specificity 98%):

1. Age at onset ≤40 years
2. Claudication of extremities
3. Decreased brachial artery pulse
4. BP difference between arms ≥10 mmHg
5. Bruit over subclavian arteries or aorta
6. Arteriographic abnormality (narrowing/occlusion of aorta, its primary branches, or large arteries in proximal extremities)

Newer ACR/EULAR Scoring (≥5 points required):

Renal Involvement (from Brenner & Rector)

• Renal disease is usually due to obliterative arteritis of the main renal artery or narrowing of renal ostia by abdominal aortitis
• Causes renovascular hypertension (40-60% of patients)
• May rarely cause mesangial proliferative glomerulonephritis, IgA nephropathy-like lesions, renal amyloidosis, or crescentic GN
• Progressive renal failure is uncommon

Cutaneous Manifestations (from Andrews' Dermatology)

• Loss of hair and skin atrophy due to ischemia
• Occasional necrotizing or granulomatous vasculitis of small vessels
• Erythema nodosum-like or erythema induratum-like nodules
• Sweet syndrome association
• Pyoderma gangrenosum-like ulcerations (especially in Japan; lesions precede TA diagnosis by ~3 years on average)

Treatment

• Prednisone 1 mg/kg/day, tapered over 8-12 weeks to ≤20 mg/day
• Relapse is common when steroids are tapered

• Methotrexate
• Mycophenolate mofetil (MMF)
• Azathioprine

• IV pulsed cyclophosphamide

• TNF-α antagonists (infliximab, etanercept): complete remission in 37%, partial in 53.5%
• Tocilizumab (anti-IL-6R): initial trial showed beneficial effect; now increasingly used - note that tocilizumab suppresses CRP synthesis, complicating disease monitoring
• Rituximab, abatacept, and ustekinumab have also been used

• Aneurysmal enlargement with rupture risk
• Severe aortic regurgitation or coarctation
• Critical limb ischemia or severe cerebrovascular disease
• Uncontrolled hypertension from renal artery stenosis
• Surgery should be delayed until immunosuppression achieves remission

Prognosis

• Survival at 15 years: >95% in most Western/Japanese cohorts
• Survival falls to ~67% in patients with serious complications or progressive disease course
• 74% report compromised daily activities; 23% unable to work
• Follow-up should include angiographic monitoring with MRI (preferred over CT to avoid cumulative radiation)

Cellulitis - Treatment

Overview

Fig. Cellulitis - intense erythema with blistering and lymphangitis of the lower leg (Andrews' Diseases of the Skin)

Step 1 - Distinguish Purulent vs. Non-Purulent

• Use ultrasound if abscess is clinically uncertain - abscess appears as a fluid-filled cavity; cellulitis shows "cobblestoning" with hypoechoic reticular stranding
• Mark the skin perimeter with an indelible marker to track spread at follow-up

Step 2 - Assess Severity

Non-Purulent Cellulitis Treatment

Caused predominantly by Group A Streptococcus; MRSA coverage generally NOT required

Mild (Outpatient - Oral):

• Cephalexin 500 mg four times daily × 10 days (first choice)
• Dicloxacillin 500 mg four times daily × 10 days
• Penicillin VK 500 mg four times daily × 10 days (streptococcal)
• Clindamycin 300-450 mg four times daily × 10 days

5-day regimens have been successful where follow-up at day 5 is feasible

Moderate (IV Required):

• Penicillin G IV
• Ceftriaxone 1 g IV every 24 hours
• Cefazolin IV
• Clindamycin IV

Severe / Unclear Pathogen / Sepsis:

• Vancomycin (15-20 mg/kg IV q12h) + imipenem 500 mg IV q6h
• Or vancomycin + piperacillin-tazobactam 4.5 g IV q6h
• Or vancomycin + meropenem 500-1000 mg IV q8h
• Transition to oral once clinical response achieved

Purulent Cellulitis Treatment (incl. Abscess)

Target: MRSA-active agents

Mild (Drainable abscess, no systemic signs):

• Incision and drainage (I&D) alone - no antibiotics needed in immunocompetent patients if drainage is complete
• Wound culture recommended if antibiotics are given

Moderate (Purulent cellulitis without systemic signs, or abscess with mild-moderate systemic signs) - Oral:

• TMP-SMX DS (trimethoprim-sulfamethoxazole) 1-2 tablets PO twice daily × 7-10 days (preferred for MRSA)
• Doxycycline 100 mg PO twice daily × 7-10 days
• Clindamycin 300-450 mg PO four times daily × 7-10 days

Severe (Systemic signs, sepsis, or immunocompromised) - IV:

• Vancomycin 15 mg/kg IV q12h (MRSA coverage)
• Linezolid 600 mg IV q12h
• Daptomycin 4 mg/kg IV q24h
• Telavancin 10 mg/kg IV q24h
• Clindamycin 600 mg IV q8h

• Piperacillin-tazobactam 4.5 g IV q6h, OR
• Meropenem 500-1000 mg IV q8h, OR
• Imipenem-cilastatin IV

Special Situations

Freshwater exposure (Aeromonas sp.):

• Doxycycline 100 mg IV q12h + Ceftriaxone 1 g IV q24h

Saltwater exposure (Vibrio sp.):

• Doxycycline 100 mg IV q12h + Ceftriaxone 1 g IV q24h

Penicillin allergy:

• Non-IgE-mediated: first-generation cephalosporin (cephalexin) is acceptable
• IgE-mediated anaphylaxis: use clindamycin, linezolid, or vancomycin

Admission Criteria

• Systemic toxicity (fever, tachycardia, hypotension)
• Comorbidities: diabetes, alcoholism, immunosuppression
• Failed outpatient oral antibiotics
• Unable to tolerate oral medication
• Sepsis - consider ICU admission

Secondary Prevention (Recurrent Cellulitis)

• Prophylactic Penicillin V 250 mg orally twice daily - effective for patients with chronic lymphedema and ≥3 episodes per year
• Treat tinea pedis aggressively (common portal of entry on the leg)
• Compression therapy to reduce lymphedema
• A 2026 systematic review (PMID 41275489) confirms compression and antibiotic prophylaxis as the main strategies for secondary prevention

Response Monitoring

• Most cases improve within 4-6 days
• Mark skin margin with pen at baseline - if erythema spreads beyond the mark within 24-48 hours of therapy, reassess for necrotizing fasciitis, deeper infection, or treatment failure
• Do NOT mistake bilateral lower leg stasis dermatitis, contact dermatitis, or eosinophilic cellulitis (insect bite reaction) for cellulitis - these mimics are common causes of over-diagnosis