Rheumatology





Learning Rheumatology
  • Understanding Mechanism of Action: 
    • 1. Name 2 rheumatological medications that are contraindicated or used with caution in patients on Azathioprine, and Why so?
      • Allopurinol, and 
    • Why does Rituximab work in RA?
      • B-cell activation occurs in RA. Of note, it is T-cell dependent. 
  • Understanding Pathogenesis
    • How do you differentiate SLE flare up vs Infections in patients with SLE? Why so?
      • CRP normal in flare up, elevated in Infections
      • CRP is high in RA as Th1 pathway is involved. 
    • How do you differentiate between Type I, Type II, Type III cryoglobunimia? 
      • Type I: M component present (Monocolnal Ig G or IgM); RF - (no Polyclonal Ig G)
      • Type II: M component present (Monoclonal Ig G or Ig M) RF + (as polyclonal Ig G is also present along with M protein)
      • Type III:M component absent (Polyclonal Ig G) RF + (Polyclonal Ig G)
    • How does RA and Gout cause erosions, but SLE does not?
      • Needs to verify but my conceptual answer is: Inflammatory mediators in Gout and RA activate degrading enzymes that cause joint erosions, but such enzymes are not activated in SLE!
        • SLE:
          • BLyS, IL -6, IL -1, TNF - alpha (please note these cytokines are also seen in RA and Gout) are involved in inflammatory process and tissue injury in a patient with SLE. 
            • But, this is not a Th1 mediated response (hence, CRP is normal). Does Th1 and Th2 pathway both lead to activation of same cytokines IL-1,6, TNF alpha. If then, why should CRP be normal in one, increased in other. 
        • RA
        • Gout:
          • 3 Pathway ends in recruitment of inflammatory cell
            • 1 and 2. IL 1 - B Mediated 
              • 1. Activates TNF alpha, IL-6, IL-8
              • 2. IL-1 receptor activation in synovial cells, that produce more chemokines.  
            • 3 (IL- B independet)
              • Monosodium urate activates C5-C9 directly that intern generates more TNF -Alpha, IL-6, IL-8
          • Needs verification: Does these cells activation eventually leads to activation of enzymes that are activated in RA or Not? 
          • Figure 1. Mechanisms of Inflammation in Gout. NEJM 2011
    • How is the pathogenesis of Scleroderma different than RA, and Gout?
      • In RA and Gout (either auto-antigen, or monosodium urate) leads to activation of inflammatory cells and enzymes. 
      • In Scleroderma, on the other hand, early microvascular damage, mononuclear-cell infiltrates, and slowly developing fibrosis is the main disease process. 
    • Which Immune axis pathway is blocked by Steroids in PMR / GCA? 
      • There are two major immune response network in PMR-GCR.
        • 1. IL-12 - Th1 - IFN-Y axis
          • The cells leading to this axis activation is not seen in temporal artery biopsy of a patient with PMR alone. This axis is however seen in a patient with GCA along with IL -6 - IL 17/ IL 21 axis. 
        • 2. IL -6 - Th17 - IL 17, Il- 21 axis
        • The latter, but nor former axis is effectively suppressed by steroids
        • These pathway leads to proteolytic enzyme activation and growth promoting factors (VEGF, PDGF). The action of proteolytic enzyme, and growth promoting factors promotes arterial wall remodeling  
        • IL -6 is a major stimulant of CRP production. Hence, it is elevated in GCA/PMR. Hence, CRP acts as a surrogate marker of IL-6 level. 
    • What is the cytokine mostly involved in CRP production. 
    • What are the final main mediators of inflammation in RA, JRA, AOSD?
      • RA: TNF -alpha, IL-6
      • JRA, AOSD: IL-1
    • How to differentiate classic complement pathway activation vs alternate pathway?
      • Classic Pathway: Decrease C4, Decreased C3
      • Alternate Pathway: Normal C4, Decreased C4
    • Why are opiates relatively ineffective in Fibromyalgia?
      • Due to hyperactive endogenous opoiod system. Low dose Naloxone hence may work.