Rheumatology‎ > ‎

Vasculitides / Including PMR

    • Non-palpable
      • Primary Cutaneous Ds (Trauma, Solar Purpura, Steroids)
      • Systemic Ds 
        • Coagulation abnormalities (Thrombocytopenia, Abnormal platelet function, Warfarin reaction, clotting factor defects, DIC)
        • Vascular Fragility (Scurvy, Amyloidosis, Ehlers-Danlos syndrome)
        • Emboli (Fat, cholesterol) 
    • Palpable(due to vessel wall inflammation)
      • Infection (Endocarditis, RMSF, Disseminated Gonoccocemia, Acute Menigococcemia)
      • Non-infectious inflammatory i.e Vasculitis (see below in vasculitis)
    • References: 

      Case 22-2011: A 79-Year-Old Man with a Rash, Arthritis, and Ocular Erythema (Small Vessel Vasculitis)

      Pathophysiology of Vasculitides (Harrisons')
      3 main mechanisms 
      • Pauciimmune or ANCA associated : GPA, E-GPA, MPA
      • Immune Complex formation or deposition: HSP(IgA), SLE, Hep-B, Hep-C Cryoglubunemic, Serum sickness with cutaneous vasculitis)
      • Pathogenic T- Lymbhocytes and granuloma formation: Giant cell, Takayasu, GPA, E-GPA


      Case 7-2015: A 25-Year-Old Man with Oral Ulcers, Rash, and Odynophagia

      • GCA
        • 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, Blindnes
        • Symptoms:
        • Signs:
        • Labs: 
          • ESR (Sensitivity 84%) CRP  (Sensitivity 86%) 
          • 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 Vasculitides
          • 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 can be used to visualize superficial arteries, such as the temporal artery (limited use for deeper vessels)
        • 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 arteritides (e.g., ANCA-associated vasculitis). 
          • Biopsy identifies 85 to 95% of cases. Hence, a negative biopsy finding does not rule out giant-cell arteritis 
      Scalp Necrosis Associated with Giant-Cell Arteritis NEJM 2016
      • PMR
          • Epidemiology:
            • Peak incidences at the age of 70 to 80 years; age (50 years or older) is considered a criterion for the diagnosis. 
              • Incidenc: 
                • 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 subacromial, 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) 
        • Lab: 
          • CRP, ESR, Anemia, Thrombocytosis
          • In selective patients consider: TSH, Ca, RF, Anti-CCP, ANCA, CPK , SPEP, UPEP, FLC, UA, LFT. 
        • References: 
      • Type
        • Type I (M spike +, RF -)
        • Type II (M spike +, RF +)
        • Type III (M spike -, RF +)
      Lancet 2012
      • 2 main pathogenesis leading to organ damage and clinical manifestations
        • Cryoglobulinaemic Vasculitis: Immune-complex mediated activation of classic complement pathway (usually by type II i.e Mixed cryo)
        • Hyper-viscosity syndrome, leading to Vascular slugging, mainly by type I Cryo
          • Neurological (headache, confusion)
          • Ocular (blurry vision, visual loss)
          • Rhino-otological (epistaxis, hearing loss) 
          • Rapidly progressive Renal Failure 
          • Treatment:
            • Urgent 
            • Needs Plasma Exchange 
        • IgM and IgG can only activate complement system, hence cryoglobulinemic disorders are either IgG or IgM mediated.

      The most common clinical manifestations of cryoglobulinemic vasculitis are cutaneous vasculitis, arthritis, peripheral neuropathy, and glomerulonephritis. Renal disease develops in 10–30% of patients. Life-threatening rapidly progressive glomerulonephritis or vasculitis of the CNS, gastrointestinal tract, or heart occurs infrequently.
      • Clinical feature:
      • When to suspect 
      Lancet 2012

      Appreciate that all 3 Cryoglobulinemia types (Type I, Type II, Type III) as a cause Immune-Complex-mediated GN with low complement levels as a cause of RPGN

      This is an example of cryoglobuminemia as an example of complement mediated disease causing RPGN.
      Appreciate in B:
      • There is IgM, Kappa and IgG bands that are prominent. IgM, and Kappa has 2 prominent bands each. Likely 2 clones are involved. IgG on the other hand is polyclonal. 
      • Because this patient has M-spike (IgM, Kappa), and IgG is also present it is type II (Mixed) Cryoglobunemia.