Rheumatoid arthritis Flashcards

Question

What is the goal of treatment of RA?

Answer 1

The treatment of RA is both pharmacological and non-pharmacological. The goal of treatment is to achieve remission, in any case if remission cannot be achieved we should have low disease activity

Answer 2

For the pharmacological treatment we have the medications to (1) relieve symptoms and (2) Disease Modifying Anti- Rheumatic drugs (DMARDs) Types: 1. convectional synthetic ones (csDMARDs) and 2. target synthetic ones (tsDMARDs)

Answer 3

NSAIDS(COX-1 and COX-2) Steroids Calcium Vitamin D Folic acid 10mg weekly for the patient on MTX

Answer 4

1. Methotrexate is the anchor drugs for a treatment naïve patient 2. Sulfasalazine 3. Hydroxychloroquine 4. Leflunomide 5. Gold 6. Azathioprine

Answer 5

* Methotrexate at 0.3mg/kg/week not exceeding 25mg/week (lower dose than that used for chemotherapy) * Sulfasalazine at 500mg bid not exceeding 2-3g daily * HCQ at 3-5mg/kg/day not exceeding 600mg daily

Answer 6

TNFa inhibitors Etanercept Infliximab Adalimumab Golimumab Certolizumab pegol Canakinumab(IL-1 inhibitor) Anakinra(IL-1 inhibitor) Rilonacept(IL-1 inhibitor) Tocilizumab(IL-6 inhibitor) Abatacept(costimulator inbitor) Rituximab is an anti-CD20 monoclonal antibody for treatment of Rheumatoid arthritis

Answer 7

Do an interferon gamma release essay or TB quantum test for latent TB Because TNFa inhibitors can activate latent TB First screen patients with a chest x-ray, the INF gamma release assay and then TB quantiferon

Answer 8

Target DMARDs Tofacitinib Baricitinib Upadacitnib

Answer 9

MTX resembles folic acid and is a competitive inhibitor of folate-dependent enzymes, such as dihydrofolate reductase (DHFR). These enzymes are involved in pyrimidine (DNA) synthesis and de novo purine synthesis of DNA and RNA. DHFR inhibition by MTX leads to depletion of tetrahydrofolates that are essential for DNA, RNA and protein synthesis The mechanisms by which MTX exerts its effects are complex and not yet fully known. Several mechanisms have been proposed: Inhibition of T cell proliferation due to the effects of MTX on purine and pyrimidine metabolism, Inhibition of transmethylation reactions required for the prevention of T cell cytotoxicity Interference with glutathione metabolism leading to alterations in recruitment of monocytes And other cells to the inflamed joint, and promotion of the release of the endogenous anti-inflammatory mediator adenosine

Answer 10

Etanercept is a recombinant TNF receptor that fused to a human Fc molecule creating a bivalent TNF binding agent. It has a shorter ‘on and off binding rate to TNF than the antibodies Which may account for its distinct pharmacodynamics and, perhaps also, mode of action. Etanercept is given as an SC injection in a dose of 25 mg twice a week or 50 mg once a week.

Answer 11

Rituximab is a chimeric monoclonal antibody containing humanised and murine sequences in its protein structure. It is a potent cell lytic antibody developed initially for the treatment of B cell lymphoma. On binding to cells expressing CD20, rituximab induces cell death through a variety of mechanisms that include complement-mediated lysis, antibody-dependent cellular killing and apoptosis induction. The rationale for the use of rituximab in the treatment of RA is based in its potential to reduce the synthesis of auto reactive antibodies. Such as RF and ACPA, and impair antigen presentation to T cells as well as cytokine production. Rituximab is given via infusion Rituximab has been shown to be efficacious in comparison with placebo in a variety of clinical studies. This has been translated into reproducible results in daily practice with a reasonable safety profile.

Answer 12

Three different outcomes are of particular relevance: radiographic damage, functional disability and mortality. The following markers are used for prognosis ESR CRP RF Anti-CCP Radiograhic progression High CDAI≥22

Answer 13

Articular SLE Nodal osteoarthritis Polyarticular gout Psoriatic arthritis Polymyalgia rheumatica

Answer 14

1. Due to the susceptibility genes HLA-DR1 and HLA-DR4, the immune system is no longer able to recognize citrullinated proteins 2. Antigens are taken up by antigen-presenting cells (APC), which are dendritic cells that are activated to initiate an immune response. 3. The whole complex migrates to the lymph node, where the activation of CD4+ helper T cells takes place. 4. Furthermore, the germinal centre of the lymph node contains B cells that get activated by reciprocal and sequential signals with T cells, an immunological process called **costimulation** 5. At this level, B cells undergo somatic hyper mutation and begin to proliferate and differentiate intro plasma cells that produce autoantibodies. 6. RF is an IgM antibody with a testing specificity of 85% in RA patients, which targets the Fc portion of IgG, also called the constant region.

Answer 15

Examples are (vimentin, type II collagen, histones, fibrin, fibronectin, Epstein-Barr nuclear antigen 1, α-enolase) as self-structures Normally, these proteins are harmless components of the body’s tissues, but in RA, they are mistakenly identified as foreign antigens, triggering an autoimmune response

Answer 16

Costimulation is a crucial second signal required for the activation of T cells and B cells in the immune system. It ensures that an immune response is properly regulated, preventing inappropriate activation that could lead to autoimmunity or immune suppression. Costimulation is like a double-check system in the immune response. It ensures that T cells and B cells don’t get activated by mistake, which could lead to autoimmune diseases or weak immune responses. 1. Costimulation in T Cells (T Cell Activation) For a T cell to fully activate, it needs two signals: 1. First signal → The T cell receptor (TCR) recognizes a foreign substance (antigen) presented by an antigen-presenting cell (APC) (like a dendritic cell). 2. Second signal (costimulation) → The CD28 protein on the T cell binds to CD80/CD86 on the APC. ✅ Both signals = Full T cell activation → The immune system fights off infections. ❌ Missing the second signal = T cell stays inactive (anergic) → Prevents accidental attacks on healthy cells. Example: the interaction between CD28 and CD80/86

Answer 17

Autoantibodies are proteins produced by an immune system that no longer discriminates self from non-self-structures, so self-tissues and organs are accidentally targeted. Rheumatoid Factor ( RF) and Anti-citrullinated protein autoantibodies (ACPA )are the most studied autoantibodies involved in RA.

Answer 18

ACPA is most specific RF is more sensitive

Answer 19

* Free reactive oxygen species (ROS) generated by particulate matter inhalation can activate nuclear factor kappa B (NF-KB). * Which activates T helper cell -1 (Th1) to produce tumour necrosis factor alpha (TNF-α), interleukin-1 (IL-1) and interleukin-6 (IL-6). * These cytokines promote the maturation of resting monocytes into mature dendritic cells. * This then offer auto-antigens to self-reactive T lymphocytes, causing them to move to target tissues and promote joint inflammation and erosion. * Moreover, the citrullination of arginine amino acid residues into citrullinated peptides is also aided by ROS, which promotes chronic lung disease and systemic inflammation.

Answer 20

Angiogenesis is a process of forming new blood vessels from existing ones, which also occurs in RA. In contrast to its beneficial role in many physiological processes, in RA it plays a critical role because the immune cells can migrate into the joints . Due to the increase in vascular permeability and the expression of adhesion molecules (vascular adhesion molecule 1) Furthermore, vascular endothelial growth factor (VEGF) is a proangiogenic factor located in the synovium in RA patients, which has a potent role in bone destruction as a promoter of osteoclastogenesis

Answer 21

Infliximab Because it’s highly antigenic it is given via infusion

Answer 22

Acetaminophen Hydrocortisone

Answer 23

MTX: tetratogenic (cannot be used during pregnancy) Sulfasalazine: can cause azoospermia, safe in pregnancy HCQ: safe in pregnancy

Answer 24

MTX: tetratogenic (cannot be used during pregnancy) Sulfasalazine: can cause azoospermia, safe in pregnancy HCQ: safe in pregnancy