Large Vessel Vasculitis

#Year in Review PMR 
Tocilizumab in PMR 
101 patients 
Primary: 67% vs 31% in placebo 
No GI perforations were seen in tocilizumab

IV also approved this year, previously was SubQ in 2017 (GiACTA)

  • GCA
    • Epidemiology: Age > 50 (almost never less than 50 yr)
    • Vascular Bed Affected: external carotid branches (e.g., temporal and occipital arteries), the ophthalmic, vertebral, distal subclavian, and axillary arteries, and the thoracic aorta.
    • Complications: Aneurysm, Dissection, Blindness
    • Symptoms: Careful history is vital
      • Cranial symptoms / Head and Neck Ischemic symptoms: Much easier to diagnose 
        • Rheumatology EMERGENCY : Visual sx: Amaurosis fugues, Diplopia, Visual impairment typically in one eye . Visual loss is often permanent. 
      • Atypical Presentations with no PMR or cranial symptoms (present in about 10% of patients with GCA):
        • FUO (typically low grade, but rarely can be high grade) / Type B symptoms / Weight loss / Constitutional symptoms: not much utility of temporal artery biopsy if not having headache, or visual sx; BP check in all arms, and CTA/MRA (also better if needs follow up imaging - controversial topic especially if has aneurysm) /PET scan will help.  If branch vessels are not involved BP will be normal in all. Some patients Aorta is involved. 
          • Vessel Mural / Wall findings: More consistent with vasculitis
          • Luminal changes: Long segment of stenosis / vasculitis stenosis 
        • IUO (inflammatory disease of unknown origin)
        • Severe Anemia
        • Ischemia / Claudication of one or more extremities
        • Cough 
        • Visual changes without other cranial symptoms
    • Signs:
    • Labs: 
      • ESR (Sensitivity 84%) CRP  (Sensitivity 86%) - 5-10 % of patients will have normal inflammatory marker 
      • the specificity of these markers is at 30%. 
      • 4% patients with confirmed GCA had both a normal ESR and a normal CRP level at the time of diagnosis.
      • If clinically indicated, assays for autoantibodies (ANCA or anti–CCP), Blood Cultures (as in work up for FUO)
      • Anemia, Thrombocytosis
    • DDx: 
      • RA
      • ANCA associated Vasculitis
      • MGUS
      • FUO (all possible DDx) 
    • Imaging: 
      • MRA or CTA of AA and its major branches after giant-cell arteritis has been confirmed on biopsy to assess the extent of arterial involvement (including the presence of stenosis, dissection, and aneurysms) and to monitor vascular lesions for any signs of progression
      • Color Doppler USG (Halo sign ; but is operator dependent) can be used to visualize superficial arteries, such as the temporal artery (limited use for deeper vessels)
      • GIACTA Trial: 1/3rd of the patient had either temporal artery biopsy negative or not done, and these patients were included based on imaging 
    • Biopsy/Diagnosis 
      • In cases of suspected giant-cell arteritis, histologic verification of vasculitis should be sought by means of a temporal-artery biopsy with assessment of a vascular segment that is 1.5 to 2.0 cm in length.
      • Histology can detect small inflammatory infiltrates and can also distinguish giant-cell arteritis from non–GCA arteritis (e.g., ANCA-associated vasculitis). 
      • Biopsy identifies 85 to 95% of cases. Hence, a negative biopsy finding does not rule out giant-cell arteritis 
      • If imaging findings are suggestive, may skip the invasive biopsy in the right age group.
Scalp Necrosis Associated with Giant-Cell Arteritis NEJM 2016
    • Treatment: 
      • GIACTA Trial - Anti-IL6 (Tocilizumab)

  • PMR
      • Epidemiology:
        • Peak incidences at the age of 70 to 80 years; age (50 years or older) is considered a criterion for the diagnosis. 
          • Incidence: 
            • Higher in Whites in northern European populations (about 20/100,000 persons older than 50 years of age) 
            • Lower in southern European populations (about 10/100,000) and
            • Markedly lower in American populations of Asian or African descent (about 1/100,000) 
      • Symptoms:
        • Aching and stiffness in selected muscle groups, predominantly in the neck, shoulders, upper arms, and pelvic girdle ; most pronounced in the morning 
        • Morning stiffness lasting 30 min or longer; worsening stiffness after periods of rest.
        • Constitutional symptoms in unto 40 - 50% patients (fatigue, malaise, anorexia, weight loss, and fever (usually low-grade) 
        • Symptoms of GCA (16-21%)
        • Swelling and pitting edema of the hands and feet due to tenosynovitis (also called remitting seronegative symmetrical synovitis with pitting edema syndrome) in subset of patietns 
      • Signs: 
        • Inflammatory or degenerative arthritis, bursitis, or tendonitis 
        • Distal musculoskeletal manifestations, such as MCP joint synovitis (25% of patients) 
        • Mild synovitis can occasionally be present at the wrists and knees. 
        • Peripheral arthritis mainly affecting the wrists and knees (up to a 1/3rd patients).
        • Synovitis of the feet is typically absent in PMR
        • True muscle weakness generally does not occur, but can be difficult to assess in patients with subjective weakness related to stiffness and pain.  
      • Labs:
      • Imaging: 
        • Ultrasonography or MRI may identify sub-acromial, sub deltoid  trochanteric, and cervical bursitis and tenosynovitis of the long biceps head. 
        • Peripheral-joint synovitis should raise suspicion of an alternative diagnosis, such as rheumatoid arthritis or inflammatory osteoarthritis. 
        • However, the arthritis is typically non-erosive and responds promptly to therapy.
      • DDx: (From Panel 1 of Lancet paper; Details : See paper)
        • Rheumatological Causes (RAInflammatory Osteoarthritis, Remitting Seronegative Symmetric Synovitis with pitting edema syndrome, Connective Tissue Disease, Vasculitis (GCA, ANCA-Vasculitis), 
          • Inflammatory Myopathy: True muscle weakness present (absent in PMR)
          • Late Onset Spondyloarthopathy: Differentiated from PMR by the presence of enthesitis, dactylics, anterior uveitis, Sacrolieitis on imaging, or HLA - B27
        • Non-inflammatory Musculoskeletal Disorder (Rotator Cuff Disease, Adhesive Capsulitis, Degenerative Joint Disease, Fibromyalgia)
        • Endocrinopathies: Thyroid Disease, Parathyroid Disease
        • Infection: Viral, Bacterial (Endocarditis, Disc space Infection, Septic Arthritis), Mycobacterial (TB)
        • Malignant Disease (Solid, Hematological Disease)
        • Misc: (PD, Depression, Hypovitaminosis D, Drug Induced Myopathy)
      • Diagnostic Criteria: absence of pathognomonic clinical and laboratory characteristics makes PMR a more difficult to diagnose, unless it is accompanied by GCA. 
        • Symmetric proximal myalgias (the shoulder girdle, hip girdle, and neck muscles)combined with laboratory abnormalities underlie the diagnosis of PMR
        • Mandatory criteria:
          • Age ≥50 yr
          • Aching in both shoulders
          • Abnormal C-reactive protein level, ESR, or both
        • Additional criteria
          • Clinical Criteria
          • Morning stiffness lasting >45 min (2 points)
          • Hip pain or reduced range of motion (1 point)
          • Negative rheumatoid factor or antibodies to cyclic citrullinated peptides (2 points)
          • Absence of peripheral synovitis (1 point) 
          • USG Criteria
          • At least one shoulder with sub deltoid bursitis, biceps tenosynovitis, or glenohumeral synovitis, AND at least one hip with synovitis or trochanteric bursitis (1 point)
          • Subdeltoid bursitis, biceps tenosynovitis, or glenohumeral synovitis in bothshoulders (1 point) 
  • Differences between TA and GCA 
    • TA:< 50 yrs, GCA > 50 yrs
    • TA: HLA I disease where as GCA is a HLA II disease. 
      • Demirkaya, Erkan, Zehra Serap Arici, Micol Romano, Roberta Audrey Berard, and Ivona Aksentijevich. 2019. “Current State of Precision Medicine in Primary Systemic Vasculitides.” Frontiers in Immunology 10 (December): 2813